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

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2-Bromo-4-methoxy-1-trifluoromethoxy-benzene (Preparation 59, 19.0 g, 73.9 mmol) in anhydrous tetrahydrofuran (400 ml) was added n-butyl lithium (2.5M solution in hexanes, 44.2 ml, 110.9 mmol) while maintaining the temperature below −70° C. under an atmosphere of nitrogen. The resulting solution was stirred at −70° C. for 1 hour. Tri-isopropyl borate (20.9 g, 110.9 mmol) was added and the mixture stirred at −70° C. for an additional 2 hours. The reaction mixture was quenched with saturated ammonium chloride aqueous solution (400 ml). The resulting mixture was acidified to pH˜5 by addition of hydrochloric acid (1N aqueous solution). The layers were separated and the organic layer was washed with water (200 ml) then dried over anhydrous MgSO4 (s), filtered and evaporated in vacuo. Residue was purified by recrystallization from ethyl acetate:petroleum ether (2 ml:50 ml) to afford the title compound as a white solid (7.5 g, 43%). while maintaining the temperature below −70° C. under an atmosphere of nitrogen the mixture stirred at −70° C. for an additional 2 hours The reaction mixture was quenched with saturated ammonium chloride aqueous solution (400 ml) The resulting mixture was acidified to pH˜5 by addition of hydrochloric acid (1N aqueous solution) The layers were separated the organic layer was washed with water (200 ml) then dried over anhydrous MgSO4 (s) filtered evaporated in vacuo Residue was purified by recrystallization from ethyl acetate

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2-Bromo-4-methoxy-1-trifluoromethoxy-benzene (Preparation 59, 19.0 g, 73.9 mmol) in anhydrous tetrahydrofuran (400 ml) was added n-butyl lithium (2.5M solution in hexanes, 44.2 ml, 110.9 mmol) while maintaining the temperature below −70° C. under an atmosphere of nitrogen. The resulting solution was stirred at −70° C. for 1 hour. Tri-isopropyl borate (20.9 g, 110.9 mmol) was added and the mixture stirred at −70° C. for an additional 2 hours. The reaction mixture was quenched with saturated ammonium chloride aqueous solution (400 ml). The resulting mixture was acidified to pH˜5 by addition of hydrochloric acid (1N aqueous solution). The layers were separated and the organic layer was washed with water (200 ml) then dried over anhydrous MgSO4 (s), filtered and evaporated in vacuo. Residue was purified by recrystallization from ethyl acetate:petroleum ether (2 ml:50 ml) to afford the title compound as a white solid (7.5 g, 43%). while maintaining the temperature below −70° C. under an atmosphere of nitrogen the mixture stirred at −70° C. for an additional 2 hours The reaction mixture was quenched with saturated ammonium chloride aqueous solution (400 ml) The resulting mixture was acidified to pH˜5 by addition of hydrochloric acid (1N aqueous solution) The layers were separated the organic layer was washed with water (200 ml) then dried over anhydrous MgSO4 (s) filtered evaporated in vacuo Residue was purified by recrystallization from ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of 3-Bromo-4-trifluoromethoxy-phenol (20.0 g, 82.6 mol) and potassium carbonate (46.3 g, 330.4 mmol) in acetone (600 ml) was added drop-wise iodomethane (46.9 g, 330.4 mmol) under an atmosphere of nitrogen. The resulting mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature then filtered and the filtrate was evaporated in vacuo to afford the title compound as a colourless oil (19.8 g, 93%). at reflux for 2 hours then filtered the filtrate was evaporated in vacuo

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2-Bromo-4-methoxy-1-trifluoromethoxy-benzene (Preparation 59, 19.0 g, 73.9 mmol) in anhydrous tetrahydrofuran (400 ml) was added n-butyl lithium (2.5M solution in hexanes, 44.2 ml, 110.9 mmol) while maintaining the temperature below −70° C. under an atmosphere of nitrogen. The resulting solution was stirred at −70° C. for 1 hour. Tri-isopropyl borate (20.9 g, 110.9 mmol) was added and the mixture stirred at −70° C. for an additional 2 hours. The reaction mixture was quenched with saturated ammonium chloride aqueous solution (400 ml). The resulting mixture was acidified to pH˜5 by addition of hydrochloric acid (1N aqueous solution). The layers were separated and the organic layer was washed with water (200 ml) then dried over anhydrous MgSO4 (s), filtered and evaporated in vacuo. Residue was purified by recrystallization from ethyl acetate:petroleum ether (2 ml:50 ml) to afford the title compound as a white solid (7.5 g, 43%). while maintaining the temperature below −70° C. under an atmosphere of nitrogen the mixture stirred at −70° C. for an additional 2 hours The reaction mixture was quenched with saturated ammonium chloride aqueous solution (400 ml) The resulting mixture was acidified to pH˜5 by addition of hydrochloric acid (1N aqueous solution) The layers were separated the organic layer was washed with water (200 ml) then dried over anhydrous MgSO4 (s) filtered evaporated in vacuo Residue was purified by recrystallization from ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of 3-Bromo-4-trifluoromethoxy-phenol (20.0 g, 82.6 mol) and potassium carbonate (46.3 g, 330.4 mmol) in acetone (600 ml) was added drop-wise iodomethane (46.9 g, 330.4 mmol) under an atmosphere of nitrogen. The resulting mixture was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature then filtered and the filtrate was evaporated in vacuo to afford the title compound as a colourless oil (19.8 g, 93%). at reflux for 2 hours then filtered the filtrate was evaporated in vacuo