2-bromo-4,5-difluoroaniline

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

実験手順: To a stirred solution of 2-bromo-4,5-difluoroaniline [H. Ishikawa, T. Uno, H, Miyamoto, H. Hiraki, H. Tamaoka, M. Tominaga and K. Nakagawa, Chem. Pharm. Bull., 1990, 38(9), 2459-2462] (72 g, 34 mmol) in ether (50 mL) at 0° C. was added sodium carbonate (5.4 g, 44 mmol) and trifluoroacetic anhydride (6.2 mL, 44 mmol). The reaction mixture was stirred at room temperature for 1 h. Water (100 mL) was added and the mixture was extracted with dichloromethane (3×100 mL). The organic extracts were combined, dried (magnesium sulfate), filtered and concentrated in vacuo to give the product (9.9 g, 94%) as a white solid. IR νmax (Nujol)/cm−1 3270, 1716, 1550, 1489, 1465, 1226, 1181, 919, 876 and 821; NMR δH (400 MHz, CDCl3) 7.45-7.5 (1H, dd, J 7.5 Hz), 8.28-8.34 (1H, dd, J 8 Hz) and 8.36 (1H, br s). the mixture was extracted with dichloromethane (3×100 mL) dried (magnesium sulfate) filtered concentrated in vacuo

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

実験手順: To a stirred solution of 2-bromo-4,5-difluoroaniline [H. Ishikawa, T. Uno, H, Miyamoto, H. Hiraki, H. Tamaoka, M. Tominaga and K. Nakagawa, Chem. Pharm. Bull., 1990, 38(9), 2459-2462] (72 g, 34 mmol) in ether (50 mL) at 0° C. was added sodium carbonate (5.4 g, 44 mmol) and trifluoroacetic anhydride (6.2 mL, 44 mmol). The reaction mixture was stirred at room temperature for 1 h. Water (100 mL) was added and the mixture was extracted with dichloromethane (3×100 mL). The organic extracts were combined, dried (magnesium sulfate), filtered and concentrated in vacuo to give the product (9.9 g, 94%) as a white solid. IR νmax (Nujol)/cm−1 3270, 1716, 1550, 1489, 1465, 1226, 1181, 919, 876 and 821; NMR δH (400 MHz, CDCl3) 7.45-7.5 (1H, dd, J 7.5 Hz), 8.28-8.34 (1H, dd, J 8 Hz) and 8.36 (1H, br s). the mixture was extracted with dichloromethane (3×100 mL) dried (magnesium sulfate) filtered concentrated in vacuo

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

実験手順: To a solution of 2-bromo-4,5-difluoroaniline (100 g) and dimethyl sulfide (49 ml) in anhydrous dichloromethane (1.2 liter) is added gradually N-chlorosuccinimide (90 g) at below 15° C., and thereafter is further added in portions triethylamine (93 ml) at 15° C. After the addition, the mixture is refluxed for 7 hours. After cooling, 10% aqueous sodium hydroxide (one liter) is added to the reaction mixture, and the mixture is extracted with dichloromethane. The extract is dried over magnesium sulfate and concentrated, and the resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane=1:2). The product is recrystallized from n-hexane to give 6-bromo-3,4-difluoro-2-methylthiomethylaniline (52 g) as a white crystal, m.p. 60°-61° C. After the addition the mixture is refluxed for 7 hours After cooling the mixture is extracted with dichloromethane The extract is dried over magnesium sulfate concentrated the resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane=1:2) The product is recrystallized from n-hexane

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

実験手順: To a solution of 2-bromo-4,5-difluoroaniline (100 g) and dimethyl sulfide (49 ml) in anhydrous dichloromethane (1.2 liter) is added gradually N-chlorosuccinimide (90 g) at below 15° C., and thereafter is further added in portions triethylamine (93 ml) at 15° C. After the addition, the mixture is refluxed for 7 hours. After cooling, 10% aqueous sodium hydroxide (one liter) is added to the reaction mixture, and the mixture is extracted with dichloromethane. The extract is dried over magnesium sulfate and concentrated, and the resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane=1:2). The product is recrystallized from n-hexane to give 6-bromo-3,4-difluoro-2-methylthiomethylaniline (52 g) as a white crystal, m.p. 60°-61° C. After the addition the mixture is refluxed for 7 hours After cooling the mixture is extracted with dichloromethane The extract is dried over magnesium sulfate concentrated the resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane=1:2) The product is recrystallized from n-hexane

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

実験手順: To a solution of 2-bromo-4,5-difluoroaniline (100 g) and dimethyl sulfide (49 ml) in anhydrous dichloromethane (1.2 liter) is added gradually N-chlorosuccinimide (90 g) at below 15° C., and thereafter is further added in portions triethylamine (93 ml) at 15° C. After the addition, the mixture is refluxed for 7 hours. After cooling, 10% aqueous sodium hydroxide (one liter) is added to the reaction mixture, and the mixture is extracted with dichloromethane. The extract is dried over magnesium sulfate and concentrated, and the resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane=1:2). The product is recrystallized from n-hexane to give 6-bromo-3,4-difluoro-2-methylthiomethylaniline (52 g) as a white crystal, m.p. 60°-61° C. After the addition the mixture is refluxed for 7 hours After cooling the mixture is extracted with dichloromethane The extract is dried over magnesium sulfate concentrated the resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane=1:2) The product is recrystallized from n-hexane

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

実験手順: To a solution of 2-bromo-4,5-difluoroaniline (100 g) and dimethyl sulfide (49 ml) in anhydrous dichloromethane (1.2 liter) is added gradually N-chlorosuccinimide (90 g) at below 15° C., and thereafter is further added in portions triethylamine (93 ml) at 15° C. After the addition, the mixture is refluxed for 7 hours. After cooling, 10% aqueous sodium hydroxide (one liter) is added to the reaction mixture, and the mixture is extracted with dichloromethane. The extract is dried over magnesium sulfate and concentrated, and the resulting residue is purified by silica gel column chromatography (solvent, dichloromethane: n-hexane=1:2). The product is recrystallized from n-hexane to give 6-bromo-3,4-difluoro-2-methylthiomethylaniline (52 g) as a white crystal, m.p. 60°-61° C. After the addition the mixture is refluxed for 7 hours After cooling the mixture is extracted with dichloromethane The extract is dried over magnesium sulfate concentrated the resulting residue is purified by silica gel column chromatography (solvent, dichloromethane: n-hexane=1:2) The product is recrystallized from n-hexane

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

実験手順: To a solution of 2-bromo-4,5-difluoroaniline (100 g) and dimethyl sulfide (49 ml) in anhydrous dichloromethane (1.2 liter) is added gradually N-chlorosuccinimide (90 g) at below 15° C., and thereafter is further added in portions triethylamine (93 ml) at 15° C. After the addition, the mixture is refluxed for 7 hours. After cooling, 10% aqueous sodium hydroxide (one liter) is added to the reaction mixture, and the mixture is extracted with dichloromethane. The extract is dried over magnesium sulfate and concentrated, and the resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane=1:2). The product is recrystallized from n-hexane to give 6-bromo-3,4-difluoro-2-methylthiomethylaniline (52 g) as a white crystal, m.p. 60°-61° C. After the addition the mixture is refluxed for 7 hours After cooling the mixture is extracted with dichloromethane The extract is dried over magnesium sulfate concentrated the resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane=1:2) The product is recrystallized from n-hexane

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

実験手順: To a solution of 2-bromo-4,5-difluoroaniline (100 g) and dimethyl sulfide (40 ml) in anhydrous dichloromethane (1.2 liter) is added gradually N-chlorosuccinimide (90 g) at below 15° C., and thereafter is further added in portions triethylamine (93 ml) at 15° C. After the addition, the mixture is refluxed for 7 hours. After cooling, 10% aqueous sodium hydroxide (one liter) is added to the reaction mixture, and the mixture is extracted with dichloromethane. The extract is dried over magnesium sulfate and concentrated, and the resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane=1:2). The product is recrystallized from n-hexane to give 6-bromo-3,4-difluoro-2-methylthiomethylaniline (52 g) as a white crystal, m.p. 60°-61° C. After the addition the mixture is refluxed for 7 hours After cooling the mixture is extracted with dichloromethane The extract is dried over magnesium sulfate concentrated the resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane=1:2) The product is recrystallized from n-hexane

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

実験手順: To a stirred solution of 2-bromo-4,5-difluoroaniline [H. Ishikawa, T. Uno, H, Miyamoto, H. Hiraki, H. Tamaoka, M. Tominaga and K. Nakagawa, Chem. Pharm. Bull., 1990, 38(9), 2459-2462] (72 g, 34 mmol) in ether (50 mL) at 0° C. was added sodium carbonate (5.4 g, 44 mmol) and trifluoroacetic anhydride (6.2 mL, 44 mmol). The reaction mixture was stirred at room temperature for 1 h. Water (100 mL) was added and the mixture was extracted with dichloromethane (3×100 mL). The organic extracts were combined, dried (magnesium sulfate), filtered and concentrated in vacuo to give the product (9.9 g, 94%) as a white solid. IR νmax (Nujol)/cm−1 3270, 1716, 1550, 1489, 1465, 1226, 1181, 919, 876 and 821; NMR δH (400 MHz, CDCl3) 7.45-7.5 (1H, dd, J 7.5 Hz), 8.28-8.34 (1H, dd, J 8 Hz) and 8.36 (1H, br s). the mixture was extracted with dichloromethane (3×100 mL) dried (magnesium sulfate) filtered concentrated in vacuo