1-bromo-2-chloro-4-(trifluoromethoxy)benzene

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: A solution of sodium nitrite (16.31 g) in concentrated sulphuric acid was added dropwise to a solution of 2-chloro-4-trifluoromethoxyaniline (50 g) in acetic acid, while maintaining the temperature below 10° C. The mixture was stirred at 5°-10° C. for 0.5 hours then added slowly to a mixture of cuprous bromide (33.9 g) in aqueous hydrobromic acid (200 ml) and ice. The mixture was stirred at room temperature for 0.5 hours and left to stand overnight. The mixture was diluted with water and extracted with dichloromethane, washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness to give 2-chloro-4-trifluoromethoxybromobenzene (63.64 g) as a brown oil which was not further purified. while maintaining the temperature below 10° C The mixture was stirred at room temperature for 0.5 hours left to stand overnight extracted with dichloromethane washed with water dried (MgSO4) filtered The filtrate was evaporated to dryness

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: n-Butyllithium (2.5M in hexane, 38 ml) was added to a stirred, cooled solution of 2-chloro-4-trifluoromethoxybromobenzene (25 g) in ether while maintaining the temperature below -70° C. The mixture was stirred at -78° C. for 4 hours then poured onto solid carbon dioxide with stirring. The mixture was allowed to warm to room temperature and acidified to pH1. The layers were separated and the organic layer was washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was triturated with cyclohexane and filtered to give 2-chloro-4-trifluoromethoxybenzoic acid as a white solid mp 90.6°-91.2° C. while maintaining the temperature below -70° C with stirring to warm to room temperature The layers were separated the organic layer was washed with water dried (MgSO4) filtered The filtrate was evaporated to dryness the residue was triturated with cyclohexane filtered

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

実験手順: A solution of sodium nitrite (16.31 g) in concentrated sulphuric acid was added dropwise to a solution of 2-chloro-4-trifluoromethoxyaniline (50 g) in acetic acid, while maintaining the temperature below 10° C. The mixture was stirred at 5°-10° C. for 0.5 hours then added slowly to a mixture of cuprous bromide (33.9 g) in aqueous hydrobromic acid (200 ml) and ice. The mixture was stirred at room temperature for 0.5 hours and left to stand overnight. The mixture was diluted with water and extracted with dichloromethane, washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness to give 2-chloro-4-trifluoromethoxybromobenzene (63.64 g) as a brown oil which was not further purified. while maintaining the temperature below 10° C The mixture was stirred at room temperature for 0.5 hours left to stand overnight extracted with dichloromethane washed with water dried (MgSO4) filtered The filtrate was evaporated to dryness

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

実験手順: A solution of sodium nitrite (16.31 g) in concentrated sulphuric acid was added dropwise to a solution of 2-chloro-4-trifluoromethoxyaniline (50 g) in acetic acid, while maintaining the temperature below 10° C. The mixture was stirred at 5°-10° C. for 0.5 hours then added slowly to a mixture of cuprous bromide (33.9 g) in aqueous hydrobromic acid (200 ml) and ice. The mixture was stirred at room temperature for 0.5 hours and left to stand overnight. The mixture was diluted with water and extracted with dichloromethane, washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness to give 2-chloro-4-trifluoromethoxybromobenzene (63.64 g) as a brown oil which was not further purified. while maintaining the temperature below 10° C The mixture was stirred at room temperature for 0.5 hours left to stand overnight extracted with dichloromethane washed with water dried (MgSO4) filtered The filtrate was evaporated to dryness

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: n-Butyllithium (2.5M in hexane, 38 ml) was added to a stirred, cooled solution of 2-chloro-4-trifluoromethoxybromobenzene (25 g) in ether while maintaining the temperature below -70° C. The mixture was stirred at -78° C. for 4 hours then poured onto solid carbon dioxide with stirring. The mixture was allowed to warm to room temperature and acidified to pH1. The layers were separated and the organic layer was washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was triturated with cyclohexane and filtered to give 2-chloro-4-trifluoromethoxybenzoic acid as a white solid mp 90.6°-91.2° C. while maintaining the temperature below -70° C with stirring to warm to room temperature The layers were separated the organic layer was washed with water dried (MgSO4) filtered The filtrate was evaporated to dryness the residue was triturated with cyclohexane filtered

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: n-Butyllithium (2.5M in hexane, 38 ml) was added to a stirred, cooled solution of 2-chloro-4-trifluoromethoxybromobenzene (25 g) in ether while maintaining the temperature below -70° C. The mixture was stirred at -78° C. for 4 hours then poured onto solid carbon dioxide with stirring. The mixture was allowed to warm to room temperature and acidified to pH1. The layers were separated and the organic layer was washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was triturated with cyclohexane and filtered to give 2-chloro-4-trifluoromethoxybenzoic acid as a white solid mp 90.6°-91.2° C. while maintaining the temperature below -70° C with stirring to warm to room temperature The layers were separated the organic layer was washed with water dried (MgSO4) filtered The filtrate was evaporated to dryness the residue was triturated with cyclohexane filtered

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

実験手順: A solution of sodium nitrite (16.31 g) in concentrated sulphuric acid was added dropwise to a solution of 2-chloro-4-trifluoromethoxyaniline (50 g) in acetic acid, while maintaining the temperature below 10° C. The mixture was stirred at 5°-10° C. for 0.5 hours then added slowly to a mixture of cuprous bromide (33.9 g) in aqueous hydrobromic acid (200 ml) and ice. The mixture was stirred at room temperature for 0.5 hours and left to stand overnight. The mixture was diluted with water and extracted with dichloromethane, washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness to give 2-chloro-4-trifluoromethoxybromobenzene (63.64 g) as a brown oil which was not further purified. while maintaining the temperature below 10° C The mixture was stirred at room temperature for 0.5 hours left to stand overnight extracted with dichloromethane washed with water dried (MgSO4) filtered The filtrate was evaporated to dryness

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

実験手順: A solution of sodium nitrite (16.31 g) in concentrated sulphuric acid was added dropwise to a solution of 2-chloro-4-trifluoromethoxyaniline (50 g) in acetic acid, while maintaining the temperature below 10° C. The mixture was stirred at 5°-10° C. for 0.5 hours then added slowly to a mixture of cuprous bromide (33.9 g) in aqueous hydrobromic acid (200 ml) and ice. The mixture was stirred at room temperature for 0.5 hours and left to stand overnight. The mixture was diluted with water and extracted with dichloromethane, washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness to give 2-chloro-4-trifluoromethoxybromobenzene (63.64 g) as a brown oil which was not further purified. while maintaining the temperature below 10° C The mixture was stirred at room temperature for 0.5 hours left to stand overnight extracted with dichloromethane washed with water dried (MgSO4) filtered The filtrate was evaporated to dryness

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: n-Butyllithium (2.5M in hexane, 38 ml) was added to a stirred, cooled solution of 2-chloro-4-trifluoromethoxybromobenzene (25 g) in ether while maintaining the temperature below -70° C. The mixture was stirred at -78° C. for 4 hours then poured onto solid carbon dioxide with stirring. The mixture was allowed to warm to room temperature and acidified to pH1. The layers were separated and the organic layer was washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was triturated with cyclohexane and filtered to give 2-chloro-4-trifluoromethoxybenzoic acid as a white solid mp 90.6°-91.2° C. while maintaining the temperature below -70° C with stirring to warm to room temperature The layers were separated the organic layer was washed with water dried (MgSO4) filtered The filtrate was evaporated to dryness the residue was triturated with cyclohexane filtered

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

実験手順: A solution of sodium nitrite (16.31 g) in concentrated sulphuric acid was added dropwise to a solution of 2-chloro-4-trifluoromethoxyaniline (50 g) in acetic acid, while maintaining the temperature below 10° C. The mixture was stirred at 5°-10° C. for 0.5 hours then added slowly to a mixture of cuprous bromide (33.9 g) in aqueous hydrobromic acid (200 ml) and ice. The mixture was stirred at room temperature for 0.5 hours and left to stand overnight. The mixture was diluted with water and extracted with dichloromethane, washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness to give 2-chloro-4-trifluoromethoxybromobenzene (63.64 g) as a brown oil which was not further purified. while maintaining the temperature below 10° C The mixture was stirred at room temperature for 0.5 hours left to stand overnight extracted with dichloromethane washed with water dried (MgSO4) filtered The filtrate was evaporated to dryness

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: n-Butyllithium (2.5M in hexane, 38 ml) was added to a stirred, cooled solution of 2-chloro-4-trifluoromethoxybromobenzene (25 g) in ether while maintaining the temperature below -70° C. The mixture was stirred at -78° C. for 4 hours then poured onto solid carbon dioxide with stirring. The mixture was allowed to warm to room temperature and acidified to pH1. The layers were separated and the organic layer was washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was triturated with cyclohexane and filtered to give 2-chloro-4-trifluoromethoxybenzoic acid as a white solid mp 90.6°-91.2° C. while maintaining the temperature below -70° C with stirring to warm to room temperature The layers were separated the organic layer was washed with water dried (MgSO4) filtered The filtrate was evaporated to dryness the residue was triturated with cyclohexane filtered