1-methoxy-2-(trifluoromethyl)benzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A mixture of 8.5 g 2-trifluoromethyl anisole and 7.0 g hexamethylene tetramine was stirred at 90° C. for 1.5 hr in 80 ml trifluoroacetic acid. The reaction solution was evaporated. The resulting residue was dissolved in ethyl acetate, and it was added dropwise into ice-cooled saturated aqueous sodium bicarbonate. The ethyl acetate layer was recovered and washed with brine. It was dried over anhydrous magnesium sulfate, filtered, and evaporated. The resulting residue was purified by silica gel column chromatography to give 5.8 g of 3-trifluoromethyl-p-anisaldehyde. The reaction solution was evaporated The resulting residue was dissolved in ethyl acetate it was added dropwise into ice- cooled saturated aqueous sodium bicarbonate The ethyl acetate layer was recovered washed with brine It was dried over anhydrous magnesium sulfate filtered evaporated The resulting residue was purified by silica gel column chromatography

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

Procedure: A mixture of 10 g 2-trifluoromethyl phenol, 17 g potassium carbonate, 150 ml acetone and 7.7 ml iodomethane was heated under reflux for 2 hr. After cooling, the insoluble matters were removed by filtration, and the filtrate was evaporated. The resulting residue was dissolved in ethyl acetate, and washed with water and brine. It was dried over anhydrous magnesium sulfate, filtered, and evaporated to give 12.15 g of 2-trifluoromethyl anisole. was heated under reflux for 2 hr After cooling the insoluble matters were removed by filtration the filtrate was evaporated The resulting residue was dissolved in ethyl acetate washed with water and brine It was dried over anhydrous magnesium sulfate filtered evaporated

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

Procedure: A mixture of 8.5 g 2-trifluoromethyl anisole and 7.0 g hexamethylene tetramine was stirred at 90° C. for 1.5 hr in 80 ml trifluoroacetic acid. The reaction solution was evaporated. The resulting residue was dissolved in ethyl acetate, and it was added dropwise into ice-cooled saturated aqueous sodium bicarbonate. The ethyl acetate layer was recovered and washed with brine. It was dried over anhydrous magnesium sulfate, filtered, and evaporated. The resulting residue was purified by silica gel column chromatography to give 5.8 g of 3-trifluoromethyl-p-anisaldehyde. The reaction solution was evaporated The resulting residue was dissolved in ethyl acetate it was added dropwise into ice- cooled saturated aqueous sodium bicarbonate The ethyl acetate layer was recovered washed with brine It was dried over anhydrous magnesium sulfate filtered evaporated The resulting residue was purified by silica gel column chromatography

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

Procedure: A mixture of 10 g 2-trifluoromethyl phenol, 17 g potassium carbonate, 150 ml acetone and 7.7 ml iodomethane was heated under reflux for 2 hr. After cooling, the insoluble matters were removed by filtration, and the filtrate was evaporated. The resulting residue was dissolved in ethyl acetate, and washed with water and brine. It was dried over anhydrous magnesium sulfate, filtered, and evaporated to give 12.15 g of 2-trifluoromethyl anisole. was heated under reflux for 2 hr After cooling the insoluble matters were removed by filtration the filtrate was evaporated The resulting residue was dissolved in ethyl acetate washed with water and brine It was dried over anhydrous magnesium sulfate filtered evaporated

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

Procedure: A mixture of 8.5 g 2-trifluoromethyl anisole and 7.0 g hexamethylene tetramine was stirred at 90° C. for 1.5 hr in 80 ml trifluoroacetic acid. The reaction solution was evaporated. The resulting residue was dissolved in ethyl acetate, and it was added dropwise into ice-cooled saturated aqueous sodium bicarbonate. The ethyl acetate layer was recovered and washed with brine. It was dried over anhydrous magnesium sulfate, filtered, and evaporated. The resulting residue was purified by silica gel column chromatography to give 5.8 g of 3-trifluoromethyl-p-anisaldehyde. The reaction solution was evaporated The resulting residue was dissolved in ethyl acetate it was added dropwise into ice- cooled saturated aqueous sodium bicarbonate The ethyl acetate layer was recovered washed with brine It was dried over anhydrous magnesium sulfate filtered evaporated The resulting residue was purified by silica gel column chromatography

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

Procedure: A mixture of 8.5 g 2-trifluoromethyl anisole and 7.0 g hexamethylene tetramine was stirred at 90° C. for 1.5 hr in 80 ml trifluoroacetic acid. The reaction solution was evaporated. The resulting residue was dissolved in ethyl acetate, and it was added dropwise into ice-cooled saturated aqueous sodium bicarbonate. The ethyl acetate layer was recovered and washed with brine. It was dried over anhydrous magnesium sulfate, filtered, and evaporated. The resulting residue was purified by silica gel column chromatography to give 5.8 g of 3-trifluoromethyl-p-anisaldehyde. The reaction solution was evaporated The resulting residue was dissolved in ethyl acetate it was added dropwise into ice- cooled saturated aqueous sodium bicarbonate The ethyl acetate layer was recovered washed with brine It was dried over anhydrous magnesium sulfate filtered evaporated The resulting residue was purified by silica gel column chromatography

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

Procedure: A mixture of log 2-trifluoromethyl phenol, 17 g potassium carbonate, 150 ml acetone and 7.7 ml iodomethane was heated under reflux for 2 hr. After cooling, the insoluble matters were removed by filtration, and the filtrate was evaporated. The resulting residue was dissolved in ethyl acetate, and washed with water and brine. It was dried over anhydrous magnesium sulfate, filtered, and evaporated to give 12.15 g of 2-trifluoromethyl anisole. was heated under reflux for 2 hr After cooling the insoluble matters were removed by filtration the filtrate was evaporated The resulting residue was dissolved in ethyl acetate washed with water and brine It was dried over anhydrous magnesium sulfate filtered evaporated

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

Procedure: To a solution of 1-methoxy-2-(trifluoromethyl)benzene (6.30 g, 35.8 mmol) in THF (150 mL) was added n-BuLi (21.0 ml, 2.50 M hexane solution, 53.7 mmol), and the mixture was stirred at room temperature for 1 hr. The solution was cooled to −78° C., tris(1-methylethyl)borate (8.08 g, 43.0 mmol) was added, and the mixture was stirred at −78° C. for 0.5 hr. The reaction solution was allowed to cool to room temperature and stirred for 16 hr. The mixture was acidified with 1M hydrochloric acid and extracted with ethyl acetate (300 mL). The extract was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give a mixture (6.52 g, yield 83%) of [2-methoxy-3-(trifluoromethyl)phenyl]boronic acid and [3-methoxy-2-(trifluoromethyl)phenyl]boronic acid. The solution was cooled to −78° C. the mixture was stirred at −78° C. for 0.5 hr to cool to room temperature stirred for 16 hr extracted with ethyl acetate (300 mL) The extract was dried over anhydrous sodium sulfate filtered concentrated under reduced pressure

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

Procedure: A solution of 1-methoxy-2-(trifluoromethyl)benzene (10.0 g, 56.8 mmol) in dry chloroform (76 mL) was cooled to 0° C. and treated with chlorosulfonic acid (7.55 mL, 113.5 mmol) drop-wise under argon. After the addition was completed, the reaction mixture was gradually warmed to room temperature and stirred overnight. The reaction was quenched by pouring the mixture slowly onto ice. The separated, aqueous phase was extracted with chloroform (3×). The combined organic phase was washed sequentially with a saturated, aqueous sodium chloride solution (2×) and water. The organic phase was dried over anhydrous magnesium sulfate and concentrated in vacuo to yield the title compound (8.77 g. 31.9 mmol, 56%) as a gray solid; After the addition The reaction was quenched by pouring the mixture slowly onto ice The separated, aqueous phase was extracted with chloroform (3×) The combined organic phase was washed sequentially with a saturated, aqueous sodium chloride solution (2×) and water The organic phase was dried over anhydrous magnesium sulfate concentrated in vacuo