Methyl 2-(4-bromo-3-fluorophenyl)acetate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (4-bromo-3-fluorophenyl)acetonitrile (40 g, 0.18 mol) was dissolved in 120 mL methanol, and 65 mL concentrated sulfuric acid were added. After heating at reflux overnight, the reaction mixture was cooled, and poured into 600 mL water, and the product was extracted with CH2Cl2. The combined extracts were washed with 10% sodium carbonate solution, dried, and concentrated to afford methyl (4-bromo-3-fluorophenyl)acetate. After heating at reflux overnight the reaction mixture was cooled the product was extracted with CH2Cl2 The combined extracts were washed with 10% sodium carbonate solution dried concentrated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 2-(4-bromo-3-fluorophenyl)acetic acid (5 g, 21.46 mmol) in MeOH (50 mL) was added SOCl2 (1.879 mL, 25.7 mmol) and DMF (0.166 mL, 2.146 mmol). Then the mixture was stirred at 80° C. for 16 h. The mixture was concentrated and extracted with EA (100 mL×2) and washed with NaHCO3 (100 mL) to give the organic layer. The combined organic extract was washed with brine, dried over Na2SO4, filtered, and concentrated to yield a brown oil of methyl 2-(4-bromo-3-fluorophenyl)acetate (5 g, 17.20 mmol, 80% yield): 1H NMR (400 MHz, MeOH-d4) δ 7.53 (t, J=7.6 Hz, 1H), 7.15 (dd, J=1.6, 9.6 Hz, 1H), 7.04-6.99 (m, 1H), 3.67 (s, 3H), 3.65 (s, 2H); ES-LCMS m/z 249.0 (M+H+2). The mixture was concentrated extracted with EA (100 mL×2) washed with NaHCO3 (100 mL) to give the organic layer The combined organic extract was washed with brine dried over Na2SO4 filtered concentrated

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(4-bromo-3-fluorophenyl)acetic acid (500 mg, 2.146 mmol) in MeOH (10 mL, 247 mmol) was added sulfurous dichloride (0.232 mL, 3.22 mmol). The resulting mixture was stirred at 60° C. After 3 h, LCMS analysis showed the starting material had disappeared and the solvent was removed in vacuo. The residue was dissolved in DCM (60 mL) and washed with aqueous NaHCO3 (20 mL) and brine (20 mL). The organic layer was dried over Na2SO4, filtered and concentrated to yield a yellow oil of methyl 2-(4-bromo-3-fluorophenyl)acetate (500 mg, 1.774 mmol, 83.0% yield): 1H NMR (400 MHz, CD3OD) δ 7.53 (t, J=8.0 Hz, 1H), 7.15 (dd, J=9.8, 1.7 Hz, 1H), 7.01 (d, J=8.2 Hz, 1H), 3.75-3.61 (m, 5H); ES-LCMS m/z 248.9 (M+H). the solvent was removed in vacuo The residue was dissolved in DCM (60 mL) washed with aqueous NaHCO3 (20 mL) and brine (20 mL) The organic layer was dried over Na2SO4 filtered concentrated

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(4-bromo-3-fluorophenyl)acetic acid (500 mg, 2.146 mmol) in MeOH (10 mL, 247 mmol) was added sulfurous dichloride (0.232 mL, 3.22 mmol). The resulting mixture was stirred at 60° C. After 3 h, LCMS analysis showed the starting material had disappeared and the solvent was removed in vacuo. The residue was dissolved in DCM (60 mL) and washed with aq NaHCO3 (20 mL) and brine (20 mL). The organic layer was dried over Na2SO4, filtered and concentrated to yield a yellow oil of methyl 2-(4-bromo-3-fluorophenyl)acetate (500 mg, 1.774 mmol, 83.0% yield): 1H NMR (400 MHz, CD3OD) δ 7.53 (t, J=8.0 Hz, 1H), 7.15 (dd, J=9.8, 1.7 Hz, 1H), 7.01 (d, J=8.2 Hz, 1H), 3.75-3.61 (m, 5H); ES-LCMS m/z 248.9 (M+H). the solvent was removed in vacuo The residue was dissolved in DCM (60 mL) washed with aq NaHCO3 (20 mL) and brine (20 mL) The organic layer was dried over Na2SO4 filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (4-bromo-3-fluorophenyl)acetonitrile (40 g, 0.18 mol) was dissolved in 120 mL methanol, and 65 mL concentrated sulfuric acid were added. After heating at reflux overnight, the reaction mixture was cooled, and poured into 600 mL water, and the product was extracted with CH2Cl2. The combined extracts were washed with 10% sodium carbonate solution, dried, and concentrated to afford methyl (4-bromo-3-fluorophenyl)acetate. After heating at reflux overnight the reaction mixture was cooled the product was extracted with CH2Cl2 The combined extracts were washed with 10% sodium carbonate solution dried concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (4-bromo-3-fluorophenyl)acetonitrile (40 g, 0.18 mol) was dissolved in 120 mL methanol, and 65 mL concentrated sulfuric acid were added. After heating at reflux overnight, the reaction mixture was cooled, and poured into 600 mL water, and the product was extracted with CH2Cl2. The combined extracts were washed with 10% sodium carbonate solution, dried, and concentrated to afford methyl (4-bromo-3-fluorophenyl)acetate. After heating at reflux overnight the reaction mixture was cooled the product was extracted with CH2Cl2 The combined extracts were washed with 10% sodium carbonate solution dried concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (4-bromo-3-fluorophenyl)acetonitrile (40 g, 0.18 mol) was dissolved in 120 mL methanol, and 65 mL concentrated sulfuric acid were added. After heating at reflux overnight, the reaction mixture was cooled, and poured into 600 mL water, and the product was extracted with CH2Cl2. The combined extracts were washed with 10% sodium carbonate solution, dried, and concentrated to afford methyl (4-bromo-3-fluorophenyl)acetate. After heating at reflux overnight the reaction mixture was cooled the product was extracted with CH2Cl2 The combined extracts were washed with 10% sodium carbonate solution dried concentrated

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(4-bromo-3-fluorophenyl)acetic acid (500 mg, 2.146 mmol) in MeOH (10 mL, 247 mmol) was added sulfurous dichloride (0.232 mL, 3.22 mmol). The resulting mixture was stirred at 60° C. After 3 h, LCMS analysis showed the starting material had disappeared and the solvent was removed in vacuo. The residue was dissolved in DCM (60 mL) and washed with aq NaHCO3 (20 mL) and brine (20 mL). The organic layer was dried over Na2SO4, filtered and concentrated to yield a yellow oil of methyl 2-(4-bromo-3-fluorophenyl)acetate (500 mg, 1.774 mmol, 83.0% yield): 1H NMR (400 MHz, CD3OD) δ 7.53 (t, J=8.0 Hz, 1H), 7.15 (dd, J=9.8, 1.7 Hz, 1H), 7.01 (d, J=8.2 Hz, 1H), 3.75-3.61 (m, 5H); ES-LCMS m/z 248.9 (M+H). the solvent was removed in vacuo The residue was dissolved in DCM (60 mL) washed with aq NaHCO3 (20 mL) and brine (20 mL) The organic layer was dried over Na2SO4 filtered concentrated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 2-(4-bromo-3-fluorophenyl)acetic acid (5 g, 21.46 mmol) in MeOH (50 mL) was added SOCl2 (1.879 mL, 25.7 mmol) and DMF (0.166 mL, 2.146 mmol). Then the mixture was stirred at 80° C. for 16 h. The mixture was concentrated and extracted with EA (100 mL×2) and washed with NaHCO3 (100 mL) to give the organic layer. The combined organic extract was washed with brine, dried over Na2SO4, filtered, and concentrated to yield a brown oil of methyl 2-(4-bromo-3-fluorophenyl)acetate (5 g, 17.20 mmol, 80% yield): 1H NMR (400 MHz, MeOH-d4) δ 7.53 (t, J=7.6 Hz, 1H), 7.15 (dd, J=1.6, 9.6 Hz, 1H), 7.04-6.99 (m, 1H), 3.67 (s, 3H), 3.65 (s, 2H); ES-LCMS m/z 249.0 (M+H+2). The mixture was concentrated extracted with EA (100 mL×2) washed with NaHCO3 (100 mL) to give the organic layer The combined organic extract was washed with brine dried over Na2SO4 filtered concentrated

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(4-bromo-3-fluorophenyl)acetic acid (500 mg, 2.146 mmol) in MeOH (10 mL, 247 mmol) was added sulfurous dichloride (0.232 mL, 3.22 mmol). The resulting mixture was stirred at 60° C. After 3 h, LCMS analysis showed the starting material had disappeared and the solvent was removed in vacuo. The residue was dissolved in DCM (60 mL) and washed with aqueous NaHCO3 (20 mL) and brine (20 mL). The organic layer was dried over Na2SO4, filtered and concentrated to yield a yellow oil of methyl 2-(4-bromo-3-fluorophenyl)acetate (500 mg, 1.774 mmol, 83.0% yield): 1H NMR (400 MHz, CD3OD) δ 7.53 (t, J=8.0 Hz, 1H), 7.15 (dd, J=9.8, 1.7 Hz, 1H), 7.01 (d, J=8.2 Hz, 1H), 3.75-3.61 (m, 5H); ES-LCMS m/z 248.9 (M+H). the solvent was removed in vacuo The residue was dissolved in DCM (60 mL) washed with aqueous NaHCO3 (20 mL) and brine (20 mL) The organic layer was dried over Na2SO4 filtered concentrated