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CAS No. : | 57744-67-9 | MDL No. : | MFCD00221460 |
Formula : | C8H7IO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HZTMYTXWFHBHDC-UHFFFAOYSA-N |
M.W : | 262.04 | Pubchem ID : | 2776176 |
Synonyms : |
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With tris(dibenzylideneacetone)dipalladium (0); triphenylphosphine; silver carbonate In toluene at 90℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With caesium carbonate; triphenylphosphine In toluene at 120℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With caesium carbonate; triphenylphosphine In toluene at 120℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 20℃; for 48h; Heating / reflux; | 116 To toluene 3.0mL suspension of tert-butyl 2-amino-4-phenylbenzoate 0.10g, rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl 2.3mg, palladium acetate 0.8mg and cesium carbonate 0.24g was added 2,3-dihydro-6-iodobenzo[1,4]dioxin 0.24g, and it was heated and refluxed for 24 hours. After the reaction mixture was cooled to room temperature, rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl 2.3mg and palladium acetate 0.8mg were added, and it was heated and refluxed for 24 hours. After the reaction mixture was cooled to room temperature, insoluble matter was filtrated, and ethyl acetate and 10% citric acid aqueous solution were added to it. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after washing with saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Trikonex company, Flash Tube 2008, eluent; hexane:ethyl acetate=10:1] to give tert-butyl 2-((2,3-dihydrobenzo[1,4]dioxin-6-yl)amino)-4-phenylbenzoate. Trifluoroacetic acid 3.0mL solution of the obtained tert-butyl 2-((2,3-dihydrobenzo[1,4]dioxin-6-yl)amino)-4-phenylbenzoate was stirred at room temperature for 3 hours. The solvent was removed under reduced pressure, and the obtained residue was refined by reversed-phase silica gel column chromatography [eluent; 70-100% acetonitrile/0.1% trifluoroacetic acid aqueous solution] to give 2-((2,3-dihydrobenzo[1,4]dioxin-6-yl)amino)-4-phenylbenzoic acid 5mg of a yellow solid. 1H-NMR(DMSO-d6) δ value: 4.24(4H,s),6.79-6.82(2H,m),6.88(1H,d,J=8.6Hz),6.99(1H,dd,J=8.3,1.7Hz),7 .21(1H,s),7.37-7.41(1H,m),7.43-7.47(2H,m),7.53-7.55(2H,m),7.95(1H,d,J=8.3Hz),9.46-9.54(1H,broad),12.94-13.07(1H,broad). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate In toluene at 20 - 110℃; for 24h; | 131 To toluene 3.0mL solution of tert-butyl 2-(4-fluoroanilino)-4-vinylbenzoate 0.12g were added 2,3-dihydro-6-iodobenzo[1,4]dioxin 0.20g, cesium carbonate 0.25g, tetrabutylammonium bromide 37mg and polymer-carried bis(acetato)triphenylphosphine palladium(II) 58mg at room temperature, and it was stirred at 110°C for 24 hours. After the reaction mixture was cooled to room temperature, insoluble matter was filtrated, ethyl acetate and 10% citric acid aqueous solution were added to it. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after sequential washing with 10% citric acid aqueous solution and saturated sodium chloride aqueous solution, the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Trikonex company, Flash Tube 2008, eluent; hexane:ethyl acetate=4:1] to give tert-butyl 4-((E)-2-(2,3-dihydrobenzo[1,4]dioxin-6-yl)vinyl)-2-(4-fluoroanilino)benzoate. Trifluoroacetic acid 10mL solution of the obtained tert-butyl 4-((E)-2-(2,3-dihydrobenzo[1,4]dioxin-6-yl)vinyl)-2-(4-fluoroanilino)benzoate was stirred at room temperature for 1 hour. The solvent was removed under reduced pressure to give 4-((E)-2-(2,3-dihydrobenzo[1,4]dioxin-6-yl)vinyl)-2-(4-fluoroanilino)benzoic acid 17mg of pale yellow solid. 1H-NMR(DMSO-d6) δ value: 4.24(4H,s),6.83(1H,d,J=8.3Hz),7.00-7.15(6H,m),7.20-7.26(2H,m),7.29-7.36(2H,m),7.86(1H,d,J=8.3Hz),9.60(1H,s),12.83-13.08(1H,broad). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With silver(I) chloride In N,N-dimethyl-formamide at 50℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With silver(I) chloride In N,N-dimethyl-formamide at 50℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With potassium phosphate; copper(l) iodide; N,N`-dimethylethylenediamine In 1,4-dioxane at 85℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate In 1,4-dioxane at 70℃; | 3.A Under Argon, the 6-boronate 8 (15 mg, 0.025 mmol) in dioxane (2.0 mL) was added to the flask which was charged with Pd (dppf) Cl2 (2 mg), Cs2C03 (17 mg, 0.055 MMOL), and 3,4- ethylenedioxyiodobenzene (15 mg, 0.057 mmol). The mixture was thoroughly DEGASSED by alternately connected the flask to vacuum and Argon. The resulting solution was heated to 70 °C and stirred overnight. It was diluted by EtOAc after cooled to room temperature. The solid was removed by filter through CELITE and washed by some EtOAc. Concentration to remove the solvent and the resulting residue purified by LC to give product 9. Exact Mass is 616 and LC-MS showed 617 (M++1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In tetrahydrofuran; at 20℃; for 72h; | To a mixture of bis(triphenylphosphine)palladium(II) dichloride (134 mg, 0.191 mmol), copper(I) iodide (36 mg, 0.191 mmol) and triethylamine (15 mL) in anhydrous tetrahydrofuran (65 mL) under an atmosphere of argon were sequentially added a solution of 6-iodobenzodioxane (5.00 g, 19.08 mmol) in anhydrous tetrahydrofuran (15 mL) and a solution of <strong>[766-81-4](3-bromophenyl)acetylene</strong> (3.63 g, 20.03 mmol) in anhydrous tetrahydrofuran (10 mL). The resulting solution was stirred at room temperature for 3 days. The crude mixture was diluted with ethyl acetate, washed sequentially with 1 M hydrochloric acid, water and saturated aqueous sodium hydrogen carbonate, dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography, using ethyl acetate in heptane (0-15%) as the eluent, gave the title compound in 94% yield: 1H NMR (CDCl3) 5 7.67 (t, J= 1.6 Hz5 1 H), 7.42 - 7.46 (m, 2 H), 7.21 (t, J= 8.0 Hz, 1 H), 7.01 - 7.06 (m, 2 H), 6.84 (d, J= 7.8 Hz, 1 H), 4.26 - 4.31 (m, 4 H); MS (EI) m/z 3U, 316 [M+.]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | Stage #1: 6-iodo-1,4-benzodioxane With n-butyllithium In tetrahydrofuran; hexanes at -70℃; for 0.583333h; Stage #2: With zinc(II) chloride In tetrahydrofuran; hexanes at -70 - 0℃; Stage #3: In tetrahydrofuran; hexanes at 20 - 65℃; for 24h; | 22.1 Step 1: Preparation of 4-[3-{6-[3-bromo-5-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-phenoxy]-hexyl}-(2-(2-ethoxycarbonyl-ethyl)-phenoxy)-butyric acid ethyl ester; To a solution of 3,4-ethylenedioxyiodobenzene (1.31 g, 5.0 mmol) in dry tetrahydrofuran (10 mL) was added n-butyllithium (2.2 mL, 5.5 mmol, 2.5 M) in hexanes at -70° C. for 5 minutes. After addition, some white precipitate was formed and the suspension was stirred for 30 minutes at this temperature. Then, a solution of anhydrous zinc chloride (1.64 g, 12.0 mmol) (anhydrous zinc chloride can be obtained by heating commercial zinc chloride with heat gun under high vacuum until it melts and then cool down to room temperature before dissolve) in dry tetrahydrofuran (8 mL) was added at -70° C. The resulting clear solution was allowed to warm to 0° C. by removing the cooling bath. In a separate reaction flask, bis(dibenzylidene-acetone)palladium(0) (288 mg, 0.5 mmol) and tri-tolylphosphine (608 mg, 2.0 mmol) in dry tetrahydrofuran (5 mL) was stirred for 10 min under nitrogen at room temperature and then treated with 4-{3-[6-(3,5-dibromo-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy}-butyric acid ethyl ester (2.56 g, 4.0 mmol) in dry tetrahydrofuran (10 mL) and the above freshly prepared zinc compound in dry tetrahydrofuran at room temperature. The resulting brick red suspension was heated to 60-65° C. for 24 h. Then, the reaction mixture was cooled to room temperature and then diluted with saturated ammonium chloride solution (100 mL). The organic compound was extracted into ethyl acetate (3×75 mL) and the combined organic extracts were washed with brine solution (200 mL). The organic layers were dried over anhydrous magnesium sulfate and filtration of the drying agent and concentration of the solvent gave the crude product which was purified by using an ISCO 80 g column, eluting with 0-20% ethyl acetate in hexanes to isolate 4-[3-{6-[3-bromo-5-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-phenoxy]-hexyl}-(2-(2-ethoxycarbonyl-ethyl)-phenoxy)-butyric acid ethyl ester (579 mg, 20%) as a light yellow oil: ES(+)-HRMS m/e calculated for C37H45BrO8 (M+Na)+ 719.2190, found 719.2191. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With copper(l) iodide In diethylene glycol dimethyl ether at 130℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With silver orthophosphate; C45H38N2O2; bis(dibenzylideneacetone)-palladium(0) In tetrahydrofuran at 20 - 80℃; Inert atmosphere; optical yield given as %ee; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12% | With N-iodo-succinimide; CF3COOH In acetonitrile | 3.a Step 3a. Step 3a. 6,7-Diiodo-2,3-dihydrobenzo[b][1,4]dioxine (Compound 0102-5) To a solution of 6-iodo-2,3-dihydrobenzo[b][1,4]dioxine (2 g, 14.7 mmol) in acetonitrile (60 ml) was added NIS (9.92 g, 44.1 mmol) followed by CF3COOH (3.35 g, 29.4 mmol). The mixture was stirred at room temperature overnight. The reaction mixture was concentrated and purified by column chromatography on silica gel (Petroleum ether) to provide the title compound 0102-5 as a white solid (0.7 g, 12%): 1H NMR (DMSO-d6) δ 4.21 (s, 4H), 7.34 (s, 2H). |
12% | With N-iodo-succinimide; trifluoroacetic acid In acetonitrile at 20℃; | 3.3a Step 3a. 6,7-Diiodo-2,3-dihydrobenzo[b][1,4]dioxine (Compound 0102-5) Step 3a. 6,7-Diiodo-2,3-dihydrobenzo[b][1,4]dioxine (Compound 0102-5) (0165) To a solution of 6-iodo-2,3-dihydrobenzo[b][1,4]dioxine (2 g, 14.7 mmol) in acetonitrile (60 ml) was added NIS (9.92 g, 44.1 mmol) followed by CF3COOH (3.35 g, 29.4 mmol). The mixture was stirred at room temperature overnight. The reaction mixture was concentrated and purified by column chromatography on silica gel (Petroleum ether) to provide the title compound 0102-5 as a white solid (0.7 g, 12%): 1H NMR (DMSO-d6) δ 4.21 (s, 4H), 7.34 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine In toluene at 110℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With copper(l) iodide; bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; 1,3-bis-(diphenylphosphino)propane; 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 20 - 130℃; Inert atmosphere; Autoclave; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; 2-((di-adamantan-1-yl)phosphaneyl)-1-(2,6-diisopropylphenyl)-1H-imidazole; triethylamine In 1,4-dioxane at 100℃; for 20h; Autoclave; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | Stage #1: 6-iodo-1,4-benzodioxane; malononitrile With copper(l) iodide; caesium carbonate; <i>L</i>-proline In dimethyl sulfoxide at 130℃; for 24h; Inert atmosphere; Stage #2: In dimethyl sulfoxide at 140℃; for 12h; Stage #3: With hydrogenchloride In water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94.22% | Stage #1: 6-amino-3,4-benzodioxane With hydrogenchloride; sodium nitrite In water at -5 - 0℃; for 0.5h; Inert atmosphere; Stage #2: With potassium iodide In water at 0 - 5℃; Inert atmosphere; | 4.2 2.4.2. 6-Iodo-1,4-benzodioxane (2) A mechanically stirred mixture of 6-amino-1,4-benzodioxane (5.29 g, 35 mmol) and 36 % HCl (50 mL) was cooled to -5 °C. A solution of NaNO2 (2.90 g, 42 mmol) in 20 mL H2O was cooled to 0 °C and slowly added while maintaining the temperature at -5 °C. The final solution was stirred at 0 °C for 30 min. A solution of KI (11.62 g, 70 mmol) in 30 mL H2O was added dropwise keeping the temperature between 0 and 5 °C. The resulting mixture was stirred overnight and extracted twice with diethyl ether. The organic layer was consecutively washed with a concentrated NaHSO3 solution, 5 % NaOH and water and dried over MgSO4. The solvent was removed under reduced pressure and the crude product was purified by column chromatography using silica gel and dichloromethane-hexane (3:2; v/v) as the eluent to give 2, a pale yellow oil phase (8.64 g, 94.22%). 1H NMR (500 MHz, d6-DMSO, ppm): δ 7.18 (s, 1H), 7.13 (d, J = 8.45 Hz, 1H), 6.68 (d, J = 8.45 Hz, 1H), 4.22 (s, -OCH2CH2O-, 4H). |
86% | Stage #1: 6-amino-3,4-benzodioxane With hydrogenchloride; sodium nitrite In water at 0℃; for 0.416667h; Stage #2: With urea In water for 0.25h; Stage #3: With potassium iodide In dichloromethane; water at 20℃; | 6-Iodo-2,3-dihydrobenzo[b][l,4]dioxine (S9-2).; 2,3-dihydrobenzo[b][l,4]dioxin-6-amine (S9-1; 5 g, 33 mmol) was dissolved in 10% HCl solution and cooled to 0°C. Then, 30 mL of a cold aqueous solution of NaN02 (4.6 g, 66 mmol) was added over a period of 15 min and the reaction mixture was stirred at 0°C for an additional 10 min, followed by the addition of urea (1.6 g, 27 mmol). After 15 min, 40 mL of a suspension of KI (16.5 g, 100 mmol) in water/CH2Cl2 (1:1) was added. The reaction mixture was stirred overnight at roomtemperature then extracted with CH2C12, dried over MgS0 . And condensed under reduced pressure and the residue was purified by flash chromatography (hexane:EtOAc, 100:0 to 90:10) to afford S9-2 (7.4 g, 86%) as a colorless oil. 1H NMR (500 MHz, CDC13) δ 7.28 δ (s, 1H), 7.13 (d, J= 8.5 Hz, 1H), 6.63 (d, J= 8.5 Hz, 1H), 4.27-4.24 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium t-butanolate In N,N-dimethyl-formamide at 110℃; for 24h; | 8- (7-Iodo-2,3-dihydrobenzo[b| [l,4]dioxin-6-ylthio)-9H-purin-6-amine (S9-3).; To a solution of S9-2 (1.26 g, 4.8 mmol) in DMF (15 mL) was added 8-mercaptoadenine (0.400 g, 2.4 mmol), neocuproine (0.056 g, 0.24 mmol), Cul (0.044 g, 0.24 mmol) and NatOBu (0.460 g, 4.8 mmol). The reaction mixture was stirred at 110 °C for 24h. Solids were filtered and the filtrate was condensed under reduced pressure. The residue was flash chromatographed (CHCl3:MeOH:AcOH, 60:0.5:0.5 to 30:0.5:0.5) to yield 0.578 g (80%) of intermediate coupling product (MS (ESI) m/z 301.9 [M+H]+). To 0.400 g (1.4 mmol) of this and NIS (0.945 g, 4.2 mmol) in acetonitrile (15 mL) was added TFA (540 μ, 0.800 g, 7 mmol) and the mixture Was stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue was purified by flash chromatography(CHCl3:MeOH:AcOH, 60:0.5:0.5 to 30:0.5:0.5) to give S9-3 (0.436 g, 73%). 1H NMR (DMSO-de, 500 MHz) δ 8.37 (s, 1H), 8.03 (br s, 2H), 7.47 (s, 1H), 7.10 (s, 1H), 4.25-4.27 (m, 4H); MS (ESI) m/z 427.9 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In acetonitrile at 70℃; for 15.5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With palladium diacetate; potassium carbonate; triphenylphosphine In acetonitrile at 85℃; for 2.5h; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diisopropylamine In N,N-dimethyl-formamide at 81℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With copper(l) iodide; dichlorobis(tri-O-tolylphosphine)palladium; potassium carbonate; <i>L</i>-proline In water; N,N-dimethyl-formamide for 5h; Inert atmosphere; Reflux; | General procedure for the preparation of compound 7 General procedure: To a solution of 2-methyl-4-(trimethylsilylethynyl)-thiazole (5, 5.11 mmol) in DMF (2.5 mL) was added an appropriate (hetero)aryl halide (6, 5.63 mmol, 1.1 equiv) under nitrogen. To this mixture were added PdCl2(PPh3)2 (0.042 mmol, 0.01 equiv), L-proline (0.51 mmol, 0.1 equiv), CuI (0.25 mmol, 0.05 equiv), and K2CO3 (6.24 mmol, 1.25 equiv) and water (0.15 mL). The mixture was stirred at 45-50 °C for the time mentioned in Table 3. After completion of the reaction the mixture was cooled to room temp, partitioned between EtOAc (10 mL) and 0.1 N HCl (3.0 mL). The organic layer was collected, washed with cold water (2 x 10 mL), dried over anhydrous MgSO4, filtered and concentrated under low vacuum. The residue was purified by column chromatography on silica gel using hexane-EtOAc as solvent system to give the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.19g | With copper(l) iodide; potassium carbonate; trans-1,2-cyclohexanediamine In 1,4-dioxane at 110℃; for 40h; Inert atmosphere; | B.i B.i. Rac-(4aR*,8aR*)-tert-butyl 3-(2,3-dihydrobenzo[b] [1 ,4] 1 dioxin-6-yl)-2-oxohexahydro- 2H-pyrido[4, 3-e] [1 ,3] oxazine- 7 (3H)-carboxylate: A vial was charged with K2C03 (0.22 g, 1.56 mmol, 2 eq.), Cul (0.01 g, 0.08 mmol, 0.1 eq.) and trafts-l,2-cyclohexane diamine (0.01 g, 0.08 mmol, 0.1 eq.), rac-(4aR*,8aR*)-tert-butyl 2-oxohexahydro-2H-pyrido[4,3-e][l,3]oxazine-7(3H)-carboxylate (Preparation A, 0.2 g, 0.78 mmol) and flushed with nitrogen for 5 min. A solution of 6-iodo- 2,3-dihydrobenzo[b][l,4]dioxine (0.21 g, 0.78 mmol, 1.01 eq.) in dry dioxane (0.78 mL) was added and the resulting suspension was at 110°C for 40 h. The reaction mixture was cooled to rt and filtered over Celite. The solid was washed by EA (2 x 10 mL). The filtrate was concentrated to dryness and the residue was purified by CC (DCM/MeOH 49: 1 to 19: 1) to give the title compound as a beige foam (0.19 g). MS (ESI, m/z): 391.2 [M+H+] for C20H26N2O6. |
0.19 g | With copper(l) iodide; potassium carbonate; trans-1,2-cyclohexanediamine In 1,4-dioxane at 110℃; for 40h; Inert atmosphere; | B.i B.i. Rac-(4aR*,8aR*)-tert-butyl 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-oxohexahydro-2H-pyrido[4,3-e][1,3]oxazine-7(3H)-carbox A vial was charged with K2CO3 (0.22 g, 1.56 mmol, 2 eq.), CuI (0.01 g, 0.08 mmol, 0.1 eq.) and trans-1,2-cyclohexane diamine (0.01 g, 0.08 mmol, 0.1 eq.), rac-(4aR*,8aR*)-tert-butyl 2-oxohexahydro-2H-pyrido[4,3-e][1,3]oxazine-7(3H)-carboxylate (Preparation A, 0.2 g, 0.78 mmol) and flushed with nitrogen for 5 min. A solution of 6-iodo-2,3-dihydrobenzo[b][1,4]dioxine (0.21 g, 0.78 mmol, 1.01 eq.) in dry dioxane (0.78 mL) was added and the resulting suspension was at 110° C. for 40 h. The reaction mixture was cooled to rt and filtered over Celite. The solid was washed by EA (2×10 mL). The filtrate was concentrated to dryness and the residue was purified by CC (DCM/MeOH 49:1 to 19:1) to give the title compound as a beige foam (0.19 g). [0251] MS (ESI, m/z): 391.2 [M+H+] for C2H26N2O6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With tetrabutyl-ammonium chloride; palladium diacetate; sodium hydrogencarbonate; silver(I) chloride In dimethyl sulfoxide at 80℃; for 24h; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In dimethyl sulfoxide at 70℃; for 8h; | 7 4.2.7 3-Benzyl-5-(1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)vinyl)-2-oxazolidinone (2ag) General procedure: The reaction of Pd(PPh3)4 (17 mg, 0.015 mmol), K2CO3 (84 mg, 0.61 mmol), 1a (50 mg, 0.31 mmol), 6-iodo-2,3-dihydrobenzo[1,4]dioxine (92 mg, 0.35 mmol), and a balloon of carbon dioxide (about 1 L) in 2 mL of DMSO afforded 89 mg of 2ag (84%) as an oil (petroleum ether/ethyl acetate=4:1): 1H NMR (300 MHz, CDCl3) δ 7.38-7.24 (m, 3H, ArH), 7.23-7.12 (m, 2H, ArH), 6.85-6.70 (m, 3H, ArH), 5.43 (s, 1H, one proton of C=CH2), 5.39-5.29 (m, 2H, one proton of C=CH2 and OCH), 4.46 (d, J=15.0 Hz, 1H, one proton of CH2 in Bn), 4.33 (d, J=15.3 Hz, 1H, one proton of CH2 in Bn), 4.22 (s, 4H, OCH2CH2O), 3.56 (t, J=8.7 Hz, 1H, one proton of NCH2 in oxazolidinone ring), 3.06 (t, J=7.5 Hz, 1H, one proton of NCH2 in oxazolidinone ring); 13C NMR (75 MHz, CDCl3) δ 157.6, 144.2, 143.7, 143.4, 135.4, 130.3, 128.7, 127.80, 127.76, 119.5, 117.3, 115.3, 112.7, 73.4, 64.25, 64.17, 49.2, 48.0; MS (m/z) 337 (M+, 15.59), 293 (M+-CO2, 11.13), 91 (100); IR (neat, cm-1) ν 1753, 1578, 1505, 1431, 1294, 1251, 1194, 1100, 1060; HRMS calcd for C20H19NO4 (M+): 337.1314, found 337.1314. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; copper (II)-fluoride; palladium diacetate In acetone at 100℃; for 24h; Inert atmosphere; Schlenk technique; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With potassium acetate; sodium hydrogencarbonate In water at 120℃; for 20h; Inert atmosphere; Autoclave; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With copper(II) ferrite; caesium carbonate In dimethyl sulfoxide at 100℃; for 20h; Inert atmosphere; | Representative experimental procedure for the synthesis of N-substituted pyrroles: General procedure: To astirred solution of: Aryl iodide (1.0 mmol), trans-4-Hydroxy-L-proline (1.5 mmol), nano CuFe2O4 (0.01 mmol), base (2 equiv), solvent (3.0 mL), 20h, 100 oC. The progress of the reaction was monitored by TLC. After the reaction was complete CuFe2O4 nano were placed on the bottom of the flask by a neodymium magnet, and the supernatant solution was removed. The crude residue was extracted with ethyl acetate (3 x 10 mL). The combined organic layers were extracted with water, saturated brine solution, and dried over anhydrous Na2SO4.The organic layers were evaporated under reduced pressure and the resulting crude product was purified by column chromatography to give the corresponding N-substituted pyrrole in excellent yields. The identity and purity of the product were confirmed by 1H,13C NMR, and mass spectra. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With sulfuric acid; palladium diacetate; caesium carbonate; sodium sulfite; tris[tert-butyl]phosphonium tetrafluoroborate In 1,4-dioxane at 80℃; for 16h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With 2,2,6,6-tetramethylpiperidylzinc chloride lithium chloride; bis(dibenzylideneacetone)-palladium(0); ruphos In tetrahydrofuran at 70℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60.6% | With copper(l) iodide; 1,10-Phenanthroline; potassium hydroxide In toluene at 125℃; for 24h; Inert atmosphere; | 4.6 2.4.3. 4-Bromo-N,N-bis(4-methoxyphenyl)aniline (3) General procedure: To a stirred solution of 4-iodoanisole (5.85 g, 25 mmol), 4-bromoaniline (1.72 g, 10 mmol), and 1,10-phenanthroline (0.18 g, 1 mmol) in toluene (100 mL) were added potassium hydroxide (5.61 g, 100 mmol) and copper(I) iodide (0.19 g, 1 mmol). The reaction mixture was heated under reflux for 24 h at 125 °C. The crude product was extracted into dichloromethane, and the organic layer was washed with 1 N HCl solution, brine, and water. The organic layer was dried with anhydrous MgSO4 and then the solvent was removed in vacuo. The residue was purified by column chromatography using silica gel and dichloromethane-hexane (1:1; v/v) as the eluent to give 3 (2.39 g, 62.2%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With α-picoline; silver(I) acetate; palladium diacetate at 20 - 80℃; for 24h; Sealed tube; | |
76% | With α-picoline; 1,1,1,3',3',3'-hexafluoro-propanol; silver(I) acetate; palladium diacetate at 80℃; for 24h; Sealed tube; | Arylation with heteroaryl iodides General procedure for monoarylation of 25 with a heterocyclic iodide [Ar(Het)-I]: The starting material Compound 25 (0.1 mmol, 24.8 mg) , Pd(OAc)2 (10 mol%, 2.2 mg) , and AgOAc (0.2 mmol, 33.4 mg) were weighed in air and placed in a sealed tube (10 mL) with a magnetic stir bar. To the reaction mixture, aryl iodide (0.15 mmol) , 2- picoline (20 mol%, 2 μ,) , and HFIP (1.0 mL) were added. The reaction mixture was first stirred at room temperature for 10 minutes and then heated to 80 °C for 24 hours under vigorous stirring. Upon completion, the reaction mixture was cooled to room temperature, filtered with celite using DCM. The solvents were removed under reduced pressure and the resulting mixture was purified by a silica gel-packed flash chromatography column using DCM/EtOAc (1/0 to 4/1 to 2/1) as the eluent. 30a (S) -3- (2 , 3-Dihydrobenzo [b] [1 , 4] dioxin-6-yl) -2- (1 , 3-dioxoisoindolin-2-yl) ~2V-methoxy propanamide (30a) Substrate 25 was heteroarylated following the general arylation procedure. Analysis of crude reaction mixture by 1H NMR showed a > 20:1 ratio of mono- and diarylated products. After purification by column chromatography using DCM/EtOAc (1/0 to 4/1 to 2/1) as the eluent, Compound 30a was obtained as a white solid (29.0 mg, 76%) . XH NMR (600 MHz, CDC13) δ 9.23 (s, 1H) , 7.81-7.78 (m, 2H) , 7.72-7.70 (m, 2H) , 6.68 (s, 1H) , 6.65 (d, J = 7.8 Hz, 1H) , 6.60 (d, J = 7.8 Hz, 1H) , 5.02 (m, 1H) , 4.16-4.14 (m, 4H) , 3.74 (s, 3H) , 3.40 (m, 2H) ; 13C NMR (150 MHz, CDC13) δ 167.93, 166.58, 143.49, 142.54, 134.36, 131.34, 129.16, 123.63, 121.75, 117.68, 117.35, 64.51, 64.16, 54.64, 34.10; HRMS (ESI-TOF) Calcd for C20H19 2O6 [M+H]+: 383.1238; found: 383.1244. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With silver(I) acetate; palladium diacetate In toluene at 110℃; for 24h; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With copper(ll) sulfate pentahydrate; ethane-1,2-dithiol; potassium hydroxide In water; dimethyl sulfoxide at 90℃; for 20h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With silver(I) acetate; palladium diacetate In toluene at 110℃; for 24h; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With cesiumhydroxide monohydrate; palladium diacetate; bis[2-(diphenylphosphino)phenyl] ether In toluene at 80℃; for 24h; Glovebox; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With copper (II) trifluoroacetate hydrate; palladium diacetate In dimethyl sulfoxide at 130℃; for 6h; Sealed tube; Inert atmosphere; | 19 General procedure for the synthesis of aryl nitriles 1b-28b General procedure: Aryl iodide (0.7 mmol, 1 equiv), tert-butyl isocyanide (2.1 mmol, 237 μL, 3 equiv), Pd(OAc)2 (0.035 mmol, 8 mg, 5 mol %), Cu(TFA)2*xH2O (1.4 mmol, 405 mg, 2 equiv) and DMSO (2.5 mL) were added to a 15 mL sealed tube, and stirred at 130 °C for 4-12 h under nitrogen. After completion of the reaction indicated by TLC, the mixture was extracted with Et2O (510 mL). The combined organic phases was dried over Na2SO4, and concentrated under vacuum. Then the residue was purified by column chromatography on silica gel using petroleum ether (30-60 °C)/Et2O as eluant to provide the pure target product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With palladium diacetate; caesium carbonate; N-acetyl-L-isoleucine; silver carbonate at 30℃; for 36h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40 % de | With silver(I) acetate; palladium diacetate In toluene at 110℃; for 24h; Overall yield = 65 %; Overall yield = 69 mg; diastereoselective reaction; | 11 4.4. General procedure for the β-arylation of aliphatic carboxamides and the preparation of the racemic compounds 3a-l, 4a-c, 5a, 6a-f, 8a-c, 8eA-hA, 8eB-hB and enantiomerically enriched 10a-c General procedure: A mixture of the corresponding carboxamide ((±)-1a-h or (±)-1iA or 1iB or 1j-(S)) (0.25 mmol), Pd(OAc)2 (2.8 mg, 5 mol %), aryl iodide (1.0 mmol, 4 equiv) and AgOAc (92 mg, 0.55 mmol, 2.2 equiv) in anhydrous toluene (3 mL) was heated at 110 °C for 24-70 h (see the respective Tables/Schemes for the reaction time for the specific examples) under nitrogen atmosphere. After the reaction period, the reaction mixture was concentrated in vacuum and purification of the resulting reaction mixture by silica gel column chromatography furnished the corresponding β-C-H arylated racemic compounds 3a-l, 4a-c, 5a, 6a-f, 8a-c, 8eA-hA, 8eB-hB and enantiomerically enriched 10a-c (see Tables/Schemes for the reaction conditions for the specific examples). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With 1,10-Phenanthroline; palladium diacetate; caesium carbonate In toluene at 160℃; for 96h; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With tris-(dibenzylideneacetone)dipalladium(0); potassium dihydrogenphosphate; [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In N,N-dimethyl acetamide at 25℃; for 20h; Schlenk technique; Inert atmosphere; Irradiation; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran; water for 18h; Inert atmosphere; Schlenk technique; Darkness; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With silver(I) acetate; palladium diacetate In toluene at 110℃; Inert atmosphere; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate In 1,4-dioxane at 120℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With potassium carbonate In 1,4-dioxane at 120℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With palladium diacetate; potassium carbonate; Trimethylacetic acid In 1,2-dichloro-ethane at 80℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With palladium diacetate; silver carbonate; Trimethylacetic acid In 1,3,5-trimethyl-benzene at 90℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With N-(2-hydroxypyridin-3-yl)acetamide; methyl bicyclo[2.2.1]hept-2-ene-2-carboxylate; silver(I) acetate; palladium diacetate In 1,2-dichloro-ethane at 100℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With silver(I) acetate; palladium diacetate In toluene at 110℃; for 24h; Inert atmosphere; | 3 3.4 General procedure for the Pd(II)-catalyzed arylation of phenylacetamides and preparation of the compounds 4a-q/7a-f (bis arylation products), 3o,r/6a,b/8e,f/9a,b (mono arylation products) General procedure: An appropriate phenylacetamide (0.12 mmol, 1 equiv), an appropriate iodo compound (0.48 mmol, 4 equiv), Pd(OAc)2 (2.7 mg, 10 mol%), and AgOAc (50 mg, 0.3 mmol, 2.5 equiv) in anhydrous toluene (3 mL) was heated at 110 °C for 24 h under a nitrogen atmosphere. After the reaction period, the solvent was evaporated in vacuo to afford a crude reaction mixture. Purification of the crude reaction mixture by column chromatography furnished the corresponding arylated products 4a-q/7a-f (bis arylation products), 3o,r/6a,b/8e,f/9a,b (mono arylation products) (see corresponding Tables/Schemes for specific examples and reaction conditions). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 57% 2: 34% | With silver(I) acetate; palladium diacetate In toluene at 110℃; for 24h; Inert atmosphere; | 17 3.4 General procedure for the Pd(II)-catalyzed arylation of phenylacetamides and preparation of the compounds 4a-q/7a-f (bis arylation products), 3o,r/6a,b/8e,f/9a,b (mono arylation products) General procedure: An appropriate phenylacetamide (0.12 mmol, 1 equiv), an appropriate iodo compound (0.48 mmol, 4 equiv), Pd(OAc)2 (2.7 mg, 10 mol%), and AgOAc (50 mg, 0.3 mmol, 2.5 equiv) in anhydrous toluene (3 mL) was heated at 110 °C for 24 h under a nitrogen atmosphere. After the reaction period, the solvent was evaporated in vacuo to afford a crude reaction mixture. Purification of the crude reaction mixture by column chromatography furnished the corresponding arylated products 4a-q/7a-f (bis arylation products), 3o,r/6a,b/8e,f/9a,b (mono arylation products) (see corresponding Tables/Schemes for specific examples and reaction conditions). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 25% 2: 36% | With silver(I) acetate; palladium diacetate In toluene at 110℃; for 24h; Inert atmosphere; | 19 3.4 General procedure for the Pd(II)-catalyzed arylation of phenylacetamides and preparation of the compounds 4a-q/7a-f (bis arylation products), 3o,r/6a,b/8e,f/9a,b (mono arylation products) General procedure: An appropriate phenylacetamide (0.12 mmol, 1 equiv), an appropriate iodo compound (0.48 mmol, 4 equiv), Pd(OAc)2 (2.7 mg, 10 mol%), and AgOAc (50 mg, 0.3 mmol, 2.5 equiv) in anhydrous toluene (3 mL) was heated at 110 °C for 24 h under a nitrogen atmosphere. After the reaction period, the solvent was evaporated in vacuo to afford a crude reaction mixture. Purification of the crude reaction mixture by column chromatography furnished the corresponding arylated products 4a-q/7a-f (bis arylation products), 3o,r/6a,b/8e,f/9a,b (mono arylation products) (see corresponding Tables/Schemes for specific examples and reaction conditions). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With silver(I) acetate; palladium diacetate In toluene at 110℃; for 16h; Inert atmosphere; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With silver(I) acetate; palladium diacetate In toluene at 110℃; for 24h; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; tetrabutylammomium bromide; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; zinc In tetrahydrofuran at 60℃; for 12h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tetrabutylammomium bromide; potassium acetate; palladium diacetate In N,N-dimethyl-formamide at 80℃; for 5h; Inert atmosphere; Sealed tube; | General Procedure for Synthesis of the Compounds as Shown in the Scheme S3 General procedure: To a solution of tetrabutylammonium bromide (1.100 g, 3.33 mmol), potassium acetate (0.586 g, 3.57 mmol), and palladium acetate (0.025 g, 0.11 mmol) in DMF (20 mL) were added substituted iodobenzene (2.21 mmol) and 4-acetyloxystyrene (2.44 mmol). The reaction mixture was recharged with Argon and stirred at 80°C for 5 h in a sealed tube. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous NaCl and concentrated in vacuo. The residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 10:3) to afford the intermediate substituted (E)-4-styrylphenyl acetate. To a solution of triethylamine (2.0 mL) in MeOH (5 mL) was added substituted (E)-4-styrylphenyl acetate (1.36 mmol). The reaction mixture was stirred at reflux temperaturefor 3 h. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous NaCl and concentrated in vacuo. The residue was purified by column chromatography on silica gel (dichloromethane/methanol, 10:0.3) to afford pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With isoquinoline; 2-carbomethoxynorbornene; silver(I) acetate; palladium diacetate In 1,2-dichloro-ethane at 100℃; for 24h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With silver(I) acetate; palladium diacetate In toluene at 110℃; for 48h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 6-iodo-1,4-benzodioxane; ethyl 3-(1H-indol-3-yl)-2-isocyanopropanoate With palladium diacetate; triphenylphosphine; cesium pivalate In toluene at 80℃; for 5h; Inert atmosphere; Stage #2: In toluene at 80℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 20℃; for 12h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With dichloro bis(acetonitrile) palladium(II); N-((1S,2S)-1-((R)-4-isopropyl-4,5-dihydrooxazol-2-yl)-2-methylbutyl)acetamide; silver carbonate In chloroform at 80℃; for 48h; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; (R)-N-((1R)-(adamantan-1-yl)(5-(diphenylphosphanyl)-9,9-dimethyl-9H-xanthen-4-yl)methyl)-2-methylpropane-2-sulfinamide; caesium carbonate In 1,3,5-trimethyl-benzene at 60℃; for 90h; Sealed tube; Inert atmosphere; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With palladium diacetate; triethylamine; triphenylphosphine at 20 - 100℃; for 0.166667h; Ionic liquid; Microwave irradiation; Green chemistry; | Synthesis of a,b-unsaturated Weinreb amides: general methods for synthesis of N-methoxy-N-methylcinnamamide(3a) [54] General procedure: Method B (microwave reaction): To a microwave tube were added 2.00 cm3 of the ionic liquid, 0.009 g palladium(II) acetate (0.04 mmol), and 0.021 g triphenylphosphine(0.08 mmol) with a magnetic stirrer, and the reaction was stirred at room temperature for 5 min. Then, 0.3 cm3 triethylamine(2.15 mmol), 0.12 cm3 iodobenzene (1a,1 mmol), and 0.20 cm3 N-methoxy-N-methylacrylamide(2, 0.95 mmol) were added. The mixture was stirred at room temperature for 5 min and then subjected to microwave irradiation for 5 min at 100 C. After this time, the reaction mixture was cooled to room temperature, and the product was extracted by using diethyl ether (5 cm3 and2 9 10 cm3). The organic layers were combined, dried over magnesium sulphate, and evaporated in vacuo to afford N-methoxy-N-methylcinnamamide (3a), yield 94% as an orange oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 6-iodo-1,4-benzodioxane; 1-phenyl-o-carboranyl-2-methylamine With water; palladium diacetate; silver trifluoroacetate; acetic acid; Glyoxilic acid at 80℃; for 12h; Inert atmosphere; Stage #2: With sodium carbonate In tetrahydrofuran; water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With 1,4-diaza-bicyclo[2.2.2]octane; copper(I) oxide; phenylsilane; ammonia In 1-methyl-pyrrolidin-2-one at 130℃; for 24h; Sealed tube; chemoselective reaction; | General procedure for the cyanation of aryl iodide with CO2 and NH3 General procedure: Under nitrogen atmosphere, Cu2O (10 mol %), DABCO (25 mol %), and a stirring bar were added into a 10 mL oven-dried sealed glass tube (as shown in Figure S1). Then NMP (0.5 mL), aryl iodides (0.125 mmol, 1.0 equiv.) and PhSiH3 (0.75 mmol, 6 equiv.) were injected by syringe. The tube was then sealed and CO2 (0.67 mmol, 5.4 equiv., 15 mL) as well as NH3 (0.67 mmol, 5.4 equiv., 15 mL) were injected by syringe after N2 was removed under vacuum. Finally, the mixture was stirred for 24 hr in a pre-heated-to-130 °C alloyed block. After the reaction was finished, the tube was cooled to room temperature and the pressure was carefully released. The yield of were measured by GC analysis using dodecane as the internal standard or by flash chromatography on silica gel (petroleumether/ethyl acetate). |
96 %Chromat. | With ammonia; hydrogen; copper(II) nitrate In N,N-dimethyl-formamide at 160℃; for 10h; Sealed tube; | 25 Example 25: Preparation of benzodioxane-6-carbonitrile from 3,4-ethylenedioxyiodobenzene (25) Under a nitrogen atmosphere, copper nitrate (20 mol%, 4.7 mg) and magnets were added to a previously baked 10 mL glass pressure tube. Then, N,N-dimethylformamide (0.5 mL) and 3,4-ethylenedioxyiodobenzene (0.125 mmol, 1.0 equiv., 32.8 mg) were added. The pressure tube was sealed and the air inside the tube was removed and filled with carbon dioxide (5.0 equiv., 15 mL), ammonia (5.0 equiv., 15 mL) and hydrogen (5.0 equiv., 15 mL). After the addition was completed, the glass pressure tube was placed in a metal module that had been preheated to 160° C. and stirred for 10 hours. After the reaction was completed, the reaction system was cooled to room temperature and pressure was slowly released. Using dodecane as an internal standard, the gas chromatographic working curve confirmed that the yield was 96%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With 3,5-bis(trifluoromethyl)-2-hydroxypyridine; silver(I) acetate; palladium diacetate; methyl (1S)-bicyclo<2.2.1>hept-2-eno-2-carboxylate In chloroform Inert atmosphere; Heating; enantioselective reaction; | General procedure for the Pd/(+)-NBE-CO2Me catalysed enantioselective meta-C-H activation General procedure: Arene (0.10 mmol, 1.0 equiv), Pd(OAc)2 (2.2 mg, 10 μmol,10 mol%), ligand (15 mol% or 20 mol%), hydrogen phosphate (15 mol% for benzylamine substrate), aryl iodide (0.3 mmol, 3.0 equiv.) and silver acetate (50 mg, 0.30 mmol, 3.0 equiv.) were added into a 2-dram reaction vial. Solvent and (+)-NBE-CO2Me (20 mol% or 50 mol%) were added to the mixture. The vial was flushed with N2 and capped. The reaction mixture was then stirred at the selected temperature for 12-24 h. After cooling to room temperature, the mixture was filtered through Celite and eluted with ethyl acetate. The filtrate was evaporated under reduced pressure. Purification by preparative thin-layer chromatography afforded the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With silver(I) acetate; palladium diacetate In neat (no solvent) at 110℃; for 24h; Inert atmosphere; | 3.2. General experimental procedure for the multicomponent, solvent-free Pd(II)-catalyzed direct β-C-H arylation of carboxamides involving anhydrides as substrates via in situ installation of DG General procedure: A mixture of anhydride (2,1 equiv), DG (8-aminoquinoline, 3a, 1 equiv), ArI (4-6 equiv), Pd(OAc)2 (10 mol%) and AgOAc (2.2 equiv) was heated at 110 °C for an appropriate time (2-24 h, see the corresponding Tables/Schemes for exact time and other specific conditions). Then, reaction mixture was cooled to rt, filtered on celite (EtOAc was used as a washing solvent) and the filtrate was treated with aq. NaHCO3 solution and then, extracted using EtOAc. The combined organic layers were dried over anhydrous Na2SO4 and evaporated to afford the crude reaction mixture. Then, the crude reaction mixture was subjected to the column chromatographic purification (EtOAc:Hexane 20:80) to give the corresponding C-H arylated product (see the respective Tables/Schemes for the specific entries). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With silver(I) acetate; palladium diacetate In neat (no solvent) at 110℃; for 24h; Inert atmosphere; | 3.2. General experimental procedure for the multicomponent, solvent-free Pd(II)-catalyzed direct β-C-H arylation of carboxamides involving anhydrides as substrates via in situ installation of DG General procedure: A mixture of anhydride (2,1 equiv), DG (8-aminoquinoline, 3a, 1 equiv), ArI (4-6 equiv), Pd(OAc)2 (10 mol%) and AgOAc (2.2 equiv) was heated at 110 °C for an appropriate time (2-24 h, see the corresponding Tables/Schemes for exact time and other specific conditions). Then, reaction mixture was cooled to rt, filtered on celite (EtOAc was used as a washing solvent) and the filtrate was treated with aq. NaHCO3 solution and then, extracted using EtOAc. The combined organic layers were dried over anhydrous Na2SO4 and evaporated to afford the crude reaction mixture. Then, the crude reaction mixture was subjected to the column chromatographic purification (EtOAc:Hexane 20:80) to give the corresponding C-H arylated product (see the respective Tables/Schemes for the specific entries). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With silver(I) acetate; palladium diacetate In neat (no solvent) at 110℃; for 24h; Inert atmosphere; | 3.2. General experimental procedure for the multicomponent, solvent-free Pd(II)-catalyzed direct β-C-H arylation of carboxamides involving anhydrides as substrates via in situ installation of DG General procedure: A mixture of anhydride (2,1 equiv), DG (8-aminoquinoline, 3a, 1 equiv), ArI (4-6 equiv), Pd(OAc)2 (10 mol%) and AgOAc (2.2 equiv) was heated at 110 °C for an appropriate time (2-24 h, see the corresponding Tables/Schemes for exact time and other specific conditions). Then, reaction mixture was cooled to rt, filtered on celite (EtOAc was used as a washing solvent) and the filtrate was treated with aq. NaHCO3 solution and then, extracted using EtOAc. The combined organic layers were dried over anhydrous Na2SO4 and evaporated to afford the crude reaction mixture. Then, the crude reaction mixture was subjected to the column chromatographic purification (EtOAc:Hexane 20:80) to give the corresponding C-H arylated product (see the respective Tables/Schemes for the specific entries). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66.7% | With silver tetrafluoroborate; palladium diacetate In <i>tert</i>-butyl alcohol at 85℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With silver(I) acetate; palladium diacetate In toluene at 110℃; for 24h; Inert atmosphere; | 3.4. General procedure for the Pd(II)-catalyzed, 8-aminoquinoline aided β-C-H arylation of short/medium/long chain-based unnatural amino acid carboxamides (6) General procedure: A mixture of an appropriate unnatural amino acid carboxamide 6 (0.15-0.2 mmol, 1 equiv), an appropriate aryl iodide (5 equiv), Pd(OAc)2 (10 mol%) and AgOAc (2.5 equiv) in anhydrous toluene (2-3 mL) was heated at 110 °C for 15-24 h under a nitrogen atm or in a sealed tube. After the reaction period, the reaction mixture was concentrated under reduced pressure to afford a crude reaction mixture, which was purified by column chromatography on neutral alumina or silica gel (eluent EtOAc:hexane) to give the corresponding arylated amino acid (see the respective Schemes/Tables for the specific entries). 3.4.7. 3-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-4-(1,3-dioxoisoindolin-2-yl)-N-(quinolin-8-yl)butanamide (8h). The compound 8h was obtained after purification by columnchromatography on silica gel (EtOAc:hexane 40:60) as a colourlesssolid (55 mg, 74%); Rf (40% EtOAc/hexane) 0.3; mp:190e192 C; IR (DCM): 3347, 2929, 1711, 1286, 724 cm1; 1H NMR(400 MHz, CDCl3): dH 9.69 (1H, br. s), 8.79 (1H, dd, J1 4.2,J2 1.5 Hz), 8.46 (1H, dd, J1 7.6, J2 1.2 Hz), 8.10 (1H, dd, J1 8.2,J2 1.5 Hz), 7.64 (2H, dd, J1 5.4, J2 3.0 Hz), 7.54 (2H, dd, J1 5.4,J2 3.1 Hz), 7.43 (1H, dd, J1 8.2, J2 4.2 Hz), 7.39 (1H, dd, J1 8.3,J2 1.3 Hz), 7.33 (1H, t, J 8.0 Hz), 6.93 (1H, d, J 2.0 Hz), 6.70 (1H,dd, J1 8.3, J2 2.1 Hz), 6.80 (1H, d, J 8.2 Hz), 4.19 (4H, s),4.03e3.89 (3H, m), 2.97e2.88 (2H, m); 13C NMR (CDCl3, 101 MHz):dC 169.3, 168.3, 148.1, 143.6, 142.6, 138.1, 136.2, 134.2, 134.1, 133.7,131.8, 127.7, 127.2, 123.1, 121.5, 121.3, 120.7, 117.5, 116.5, 116.2, 64.3,43.4, 42.2, 40.2; HRMS (ESI) calcd for C29H24N3O5 [MH] 494.1716found 494.1696. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With silver(I) acetate; palladium diacetate In toluene at 110℃; for 24h; Inert atmosphere; | 3.4. General procedure for the Pd(II)-catalyzed, 8-aminoquinoline aided β-C-H arylation of short/medium/long chain-based unnatural amino acid carboxamides (6) General procedure: A mixture of an appropriate unnatural amino acid carboxamide 6 (0.15-0.2 mmol, 1 equiv), an appropriate aryl iodide (5 equiv), Pd(OAc)2 (10 mol%) and AgOAc (2.5 equiv) in anhydrous toluene (2-3 mL) was heated at 110 °C for 15-24 h under a nitrogen atm or in a sealed tube. After the reaction period, the reaction mixture was concentrated under reduced pressure to afford a crude reaction mixture, which was purified by column chromatography on neutral alumina or silica gel (eluent EtOAc:hexane) to give the corresponding arylated amino acid (see the respective Schemes/Tables for the specific entries). 3.4.23. 3-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-5-(1,3-dioxoisoindolin-2-yl)-N-(quinolin-8-yl)pentanamide (9d). The compound 9d was obtained after purification by column chromatography on silica gel (EtOAc:hexane 40:60) as a colourlesssolid (54 mg, 71%); Rf (40% EtOAc/hexane) 0.3; mp:142e144 C; IR (DCM): 3055, 2986, 1709, 1265, 743 cm1; 1H NMR(400 MHz, CDCl3): dH 9.65 (1H, br. s), 8.76 (1H, dd, J1 4.4,J2 1.6 Hz), 8.70 (1H, dd, J1 7.2, J2 2.0 Hz), 8.13 (1H, dd, J1 8.2,J2 1.4 Hz), 7.77 (2H, dd, J1 5.6, J2 3.2 Hz), 7.67 (2H, dd, J1 5.4,J2 3.0 Hz), 7.52e7.47 (2H, m), 7.44 (1H, dd, J1 8.2, J2 4.0 Hz),6.83e6.81 (2H, m), 6.73 (1H, d, J 8.0 Hz), 4.16e4.12 (4H, m), 3.67(2H, t, J 7.2 Hz), 3.33e3.28 (1H, m), 2.87e2.77 (2H, m), 2.24e2.12(2H, m); 13C NMR (CDCl3, 101 MHz): dC 169.7, 168.2, 148.0, 143.4,142.2, 138.2, 136.3, 136.0, 134.3, 133.7, 132.1, 127.8, 127.4, 123.0,121.5, 121.4, 120.5, 117.4, 116.5, 116.1, 64.2, 64.2, 46.1, 40.1, 36.6, 33.8;HRMS (ESI) calcd for C30H26N3O5 [MH] 508.1872 found 508.1846. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With silver(I) acetate; palladium diacetate In toluene at 110℃; for 24h; Inert atmosphere; | 3.4. General procedure for the Pd(II)-catalyzed, 8-aminoquinoline aided β-C-H arylation of short/medium/long chain-based unnatural amino acid carboxamides (6) General procedure: A mixture of an appropriate unnatural amino acid carboxamide 6 (0.15-0.2 mmol, 1 equiv), an appropriate aryl iodide (5 equiv), Pd(OAc)2 (10 mol%) and AgOAc (2.5 equiv) in anhydrous toluene (2-3 mL) was heated at 110 °C for 15-24 h under a nitrogen atm or in a sealed tube. After the reaction period, the reaction mixture was concentrated under reduced pressure to afford a crude reaction mixture, which was purified by column chromatography on neutral alumina or silica gel (eluent EtOAc:hexane) to give the corresponding arylated amino acid (see the respective Schemes/Tables for the specific entries). 3.4.46. 3-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-12-(1,3-dioxoisoindolin-2-yl)-N-(quinolin-8-yl)dodecanamide (14d). The compound 14d was obtained after purification by column chromatography on silica gel (EtOAc:hexane 40:60) as a paleyellow color liquid (64 mg, 70%); Rf (40% EtOAc/hexane) 0.3; IR(DCM): 2928, 1708, 1526, 1286, 720 cm1; 1H NMR (400 MHz,CDCl3) dH 9.68 (1H, br. s), 8.79e8.74 (2H, m), 8.15 (1H, d, J 8.2 Hz),7.85 (2H, dd, J1 5.0, J2 3.0 Hz), 7.71 (2H, dd, J1 4.8, J2 3.0 Hz),7.54e7.49 (2H, m), 7.45 (1H, dd, J1 8.3, J2 4.3 Hz), 6.80e6.78 (3H,m), 4.20 (4H, s), 3.67 (2H, t, J 7.2 Hz), 3.20e3.16 (1H, m), 2.80 (2H,d, J 7.2 Hz), 1.75e1.72 (1H, m), 1.67e1.64 (3H, m), 1.31e1.21 (12H,m); 13C NMR (CDCl3, 101 MHz): dC 170.5, 168.5, 148.0, 143.4, 141.9,138.3, 137.8,136.3, 134.5, 133.8,132.2,127.9,127.4,123.1,121.5,121.3,120.6, 117.2, 116.4, 116.0, 64.3, 64.3, 46.0, 42.0, 38.1, 36.3, 29.5, 29.4,29.1, 29.1, 28.6, 27.4, 26.8; HRMS (ESI) calcd for C37H40N3O5 [MH]606.2968 found 606.2943. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With tris-(dibenzylideneacetone)dipalladium(0); 1,2-bis(di(pentafluorophenyl)phosphino)ethane In o-xylene at 150℃; for 12h; Glovebox; Sealed tube; Inert atmosphere; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With 2,6-dimethylbenzoic acid; palladium diacetate; silver carbonate In <i>tert</i>-butyl alcohol at 120℃; for 24h; Sealed tube; Inert atmosphere; | |
65.6% | With 2,6-dimethylbenzoic acid; palladium diacetate; silver carbonate In <i>tert</i>-butyl alcohol at 120℃; for 24h; Inert atmosphere; Sealed tube; | 18.1 (1) Preparation of Intermediate 2 To a pressure flask (100 mL) equipped with a magnetic stir bar was added Compound Intermediate 1 (2.5 g, 8.19 mmol), silver carbonate (2.26 g, 8.19 mmol), Pd(OAc) 2 (184 mg, 0.82). Millimoles), 6-iodo-2,3-dihydro-1,4-benzodioxin (5.0g, 19.1mmol), 2,6-dimethylbenzoic acid (307mg, 2.05mmol) and 30mL tert Butanol. The container was flushed with argon, sealed with a crimped lid and heated to 120°C. After 24 hours, the reaction vessel was taken out of the oil bath, cooled to room temperature, and dichloromethane (50 mL) was added to the reaction mixture. The mixture was stirred well for 10 minutes, filtered to remove solids, and rinsed with dichloromethane (50 mL). The combined filtrates were concentrated under reduced pressure, and the residue was purified by column chromatography to obtain Intermediate 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With trifluorormethanesulfonic acid; palladium diacetate; silver trifluoroacetate; acetic acid; glycine; at 100℃; for 24h;Sealed tube; | General procedure: A sealed tube with magnetic stir bar was charged with substrate 1 (0.24 mmol), glycine (0.1 mmol, 7.5 mg), Pd(OAc)2 (0.02 mmol, 4.45 mg), AgTFA (0.24 mmol, 53.01 mg) and 2 (0.2 mmol) under air. After addition of AcOH (2 mL) as solvent, TfOH (0.1 mmol, 15.0 mg) was added. The reaction mixture was allowed to stir at 100 C for 24 hours. Upon completion, the reaction mixture was cooled to room temperature, diluted with DCM, and then extracted with saturated NaHCO3 aqueous solution. The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo. The crude residue was purified by column chromatography on silica gel using PE as the eluent to afford the desired products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With triethylamine In N,N-dimethyl-formamide at 100℃; for 3h; Inert atmosphere; Autoclave; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With potassium phosphate; copper(l) iodide; ethylene glycol In isopropyl alcohol at 85 - 90℃; for 24h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With nickel(II) bromide dimethoxyethane; potassium fluoride; 4,4'-dimethyl-2,2'-bipyridines; diethoxymethylsilane In N,N-dimethyl-formamide at 25℃; for 48h; Inert atmosphere; Sealed tube; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With potassium phosphate; copper(l) iodide; N,N-dimethylethylenediamine In 1,4-dioxane at 110℃; Inert atmosphere; | 1 Synthesis of 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-(hydroxymethyl)pyridin-2(1H)-one To a solution of 3-(hydroxymethyl)pyridin-2(1H)-one (5 g, 39 960 mmol) in 1,4-dioxane (50 mL) was added 6-iodo-2,3-dihydrobenzo[b][1,4]dioxine (12.566 g, 47.952 mmol), Cul (765 mg, 3.996 mmol), K3PO4 (16.964 g, 79.920 mmol) and N,N-dimethylethylenediamine (929 mg, 7.992 mmol) under N2 atmosphere. The resulting mixture was maintained under nitrogen and stirred at 1 10 °C for overnight. After cooling down to rt, the reaction was quenched with water (100 ml_). The resulting mixture was extracted with ethyl acetate (3 x 100 ml_). The organic layers were combined, dried over anhydrous sodium sulfate, the solids were removed by filtration and the filtrate was concentrated under reduced pressure. The crude was purified by silica gel chromatography (0 to 15% CH3OH/ CH2CI2) to afford the titled compound as a white solid (4.4 g, 42%). LC/MS: mass calcd. for CI 4HI3N04: 259.08, found: 260.15 [M+H]+. |
42% | With potassium phosphate; copper(l) iodide; N,N`-dimethylethylenediamine In 1,4-dioxane at 110℃; Inert atmosphere; | 1 Synthesis of 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-(hydroxymethyl)pyridin-2(1H)-one To a solution of 3-(hydroxymethyl)pyridin-2(1H)-one (5 g, 39.960 mmol) in 1,4-dioxane (50 mL) was added 6-iodo-2,3-dihydrobenzo[b][1,4]dioxine (12.566 g, 47.952 mmol), CuI (765 mg, 3.996 mmol), K3PO4 (16.964 g, 79.920 mmol) and N,N’-dimethylethylenediamine (929 mg, 7.992 mmol) under N2 atmosphere. The resulting mixture was maintained under nitrogen and stirred at 110 °C for overnight. After cooling down to rt, the reaction was quenched with water (100 mL). The resulting mixture was extracted with ethyl acetate (3 x 100 mL). The organic layers were combined, dried over anhydrous sodium sulfate, the solids were removed by filtration and the filtrate was concentrated under reduced pressure. The crude was purified by silica gel chromatography (0 to 15% CH3OH/ CH2Cl2) to afford the titled compound as a white solid (4.4 g, 42%). LC/MS: mass calcd. for C14H13NO4: 259.08, found: 260.15 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | Stage #1: carbon dioxide With phenylsilane In N,N-dimethyl-formamide at 60℃; for 3h; Schlenk technique; Sealed tube; Stage #2: 6-iodo-1,4-benzodioxane; phenylacetylene With (bis(tricyclohexyl)phosphine)palladium(II) dichloride; triethylamine In N,N-dimethyl-formamide Schlenk technique; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With silver(I) acetate; palladium diacetate In o-xylene at 130℃; for 24h; Inert atmosphere; | Pd(II)-Catalyzed Arylation of Carboxamides 2a/2d and Preparation of Compounds 4/6 General procedure: A mixture of an appropriate carboxamide (0.2 mmol, 1 equiv), an appropriatearyl iodide (0.8 mmol, 4 equiv), Pd(OAc)2 (4.5 mg, 10 mol%)and AgOAc (0.44 mmol, 2.0-2.2 equiv) in o-xylene (2 mL) was heatedat 130 °C for 24 h in a 10 mL capacity sealed (pressure) tube (the pressuretube was flushed with nitrogen atmosphere for 2 min and it wassealed with a PTFE-lined cap, and then the tube was heated). After thereaction period, the reaction mixture was concentrated under vacuumand purification of the resulting reaction mixture by columnchromatography on neutral alumina or silica gel (EtOAc/hexane) furnishedthe corresponding arylated carboxamide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With silver(I) acetate; palladium diacetate In o-xylene at 150℃; Inert atmosphere; | Pd(II)-Catalyzed Arylation of the Carboxamide 2b and Preparationof Compounds 5 General procedure: A mixture of carboxamide 2b (0.2 mmol, 1 equiv), an appropriate aryliodide (0.8-1.0 mmol, 4-5 equiv), Pd(OAc)2 (4.5 mg, 10 mol%) andAgOAc (0.44 mmol, 2.2 equiv) in o-xylene (2 mL) was heated at 150 °Cfor 36-48 h in a 10 mL capacity sealed (pressure) tube (the pressuretube was flushed with nitrogen atmosphere for 2 min and it wassealed with a PTFE-lined cap, and then the tube was heated). After thereaction period, the reaction mixture was concentrated under vacuumand purification of the resulting reaction mixture by columnchromatography on silica gel (EtOAc/hexane) furnished the correspondingarylated carboxamide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | Stage #1: C12H18N4OSi With 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex In tetrahydrofuran at -20℃; for 2h; Stage #2: 6-iodo-1,4-benzodioxane With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; zinc(II) chloride In tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; N–phenyl–2–(dicyclohexylphosphino)pyrrole In 1,2-dimethoxyethane at 100℃; for 24h; Sealed tube; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | Stage #1: 1-formyl-o-carborane With glycine at 40℃; for 1h; Inert atmosphere; Sealed tube; Stage #2: 6-iodo-1,4-benzodioxane With silver orthophosphate; palladium diacetate; sodium hydrogencarbonate at 80℃; for 24h; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With copper (I) iodide; tetrabutylammonium bromide; potassium hydroxide at 110℃; for 10h; Sealed tube; Glovebox; Inert atmosphere; | Experimental procedure: The CuI (0.4 mmol), TBAB (16.5 mmol), KOH (16.5 mmol), 2j (1.68 g), 2j (2.59 g) and a stirring bar were added into a tube sealing (38 mL) in glovebox. After sealed, tube sealing was brought out of the glovebox under nitrogen atmosphere. The reaction was performed at 110 °C for 10 h. After the reaction finished, the tube sealing was cooled to room temperature. After cooling, dichloromethane (30 mL) and water (30 mL) were added and the layers were separated. The aqueous layer was extracted three times with dichloromethane, the combined organic extracts were washed with water (three times) and brine. Then the organic phase was dried with MgSO4 and the solvent was concentrated to afford a yellow solid. The crude product was purified by flash column chromatography on silica gel to afford the desired 4jr as a pale yellow solid (64% yield). 1H NMR (400 MHz, CDCl3) δ 10.06 (s, 1H), 7.60-7.50 (m, 3H), 7.45-7.41 (m, 3H), 7.13-7.10 (m, 1H), 6.83-6.76 (m, 2H), 4.25-4.15 (m, 4H), 1.26 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 163.3, 152.4, 143.0, 139.6, 139.4, 133.1, 132, 127.5, 125.7, 121.4, 116.8, 112.5, 108.4, 64.2, 63.9, 34.4, 30.9. (Ref : 1) Md. A. Ali, P. Saha, T. Punniyamurthy, Synthesis 6 (2010): 908-910; 2) Chem. Eur. J. 20 (2014), 4542-4547). |
64% | With copper (I) iodide; tetrabutylammonium bromide; potassium hydroxide at 110℃; for 10h; Sealed tube; Glovebox; Inert atmosphere; | Experimental procedure: The CuI (0.4 mmol), TBAB (16.5 mmol), KOH (16.5 mmol), 2j (1.68 g), 2j (2.59 g) and a stirring bar were added into a tube sealing (38 mL) in glovebox. After sealed, tube sealing was brought out of the glovebox under nitrogen atmosphere. The reaction was performed at 110 °C for 10 h. After the reaction finished, the tube sealing was cooled to room temperature. After cooling, dichloromethane (30 mL) and water (30 mL) were added and the layers were separated. The aqueous layer was extracted three times with dichloromethane, the combined organic extracts were washed with water (three times) and brine. Then the organic phase was dried with MgSO4 and the solvent was concentrated to afford a yellow solid. The crude product was purified by flash column chromatography on silica gel to afford the desired 4jr as a pale yellow solid (64% yield). 1H NMR (400 MHz, CDCl3) δ 10.06 (s, 1H), 7.60-7.50 (m, 3H), 7.45-7.41 (m, 3H), 7.13-7.10 (m, 1H), 6.83-6.76 (m, 2H), 4.25-4.15 (m, 4H), 1.26 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 163.3, 152.4, 143.0, 139.6, 139.4, 133.1, 132, 127.5, 125.7, 121.4, 116.8, 112.5, 108.4, 64.2, 63.9, 34.4, 30.9. (Ref : 1) Md. A. Ali, P. Saha, T. Punniyamurthy, Synthesis 6 (2010): 908-910; 2) Chem. Eur. J. 20 (2014), 4542-4547). |
Tags: 57744-67-9 synthesis path| 57744-67-9 SDS| 57744-67-9 COA| 57744-67-9 purity| 57744-67-9 application| 57744-67-9 NMR| 57744-67-9 COA| 57744-67-9 structure
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P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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