(1R)-1-[4-chloro-2-(trifluoromethyl)phenyl]ethanamine

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

Procedure: To a solution of (S)-N-((R)-1 (4-chloro-2-(trifluoromethyl)phenyl)ethyl)-2-methylpropane-2-sulfinamide (14.6 g, 44.5 mmol) in methanol (25 mL) was added a solution of hydrochloric acid in p-dioxane (4.0 M in p-dioxane, 22.3 mL, 89.1 mmol), and the reaction was stirred at room temperature for 30 min. Diethyl ether was then added (400 mL) and the slurry was stirred for 10 min. The solid was collected by filtration, and washed with diethyl ether (2×200 mL). The solid was then dissolved in 5 M aqueous sodium hydroxide solution, and extracted with dichloromethane (2×100 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was used without further purification (7.8 g, 34.9 mmol, 79%, >96% ee, determined by Mosher's method). the slurry was stirred for 10 min The solid was collected by filtration washed with diethyl ether (2×200 mL) The solid was then dissolved in 5 M aqueous sodium hydroxide solution extracted with dichloromethane (2×100 mL) The combined organic layers were dried (Na2SO4) filtered concentrated in vacuo The crude product was used without further purification (7.8 g, 34.9 mmol, 79%, >96% ee, determined by Mosher's method)

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

Procedure: To a solution of (S)-N-((R)-1 (4-chloro-2-(trifluoromethyl)phenyl)ethyl)-2-methylpropane-2-sulfinamide (14.6 g, 44.5 mmol) in methanol (25 mL) was added a solution of hydrochloric acid in p-dioxane (4.0 M in p-dioxane, 22.3 mL, 89.1 mmol), and the reaction was stirred at room temperature for 30 min. Diethyl ether was then added (400 mL) and the slurry was stirred for 10 min. The solid was collected by filtration, and washed with diethyl ether (2×200 mL). The solid was then dissolved in 5 M aqueous sodium hydroxide solution, and extracted with dichloromethane (2×100 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was used without further purification (7.8 g, 34.9 mmol, 79%, >96% ee, determined by Mosher's method). the slurry was stirred for 10 min The solid was collected by filtration washed with diethyl ether (2×200 mL) The solid was then dissolved in 5 M aqueous sodium hydroxide solution extracted with dichloromethane (2×100 mL) The combined organic layers were dried (Na2SO4) filtered concentrated in vacuo The crude product was used without further purification (7.8 g, 34.9 mmol, 79%, >96% ee, determined by Mosher's method)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of the crude (S)-N-(4-chloro-2-(trifluoromethyl)benzylidene)-2-methylpropane-2-sulfinamide (26.8 g, 86.0 mmol) in dichloromethane (290 mL) at −48° C. was added a solution of methyl magnesium bromide (3.0 M in diethyl ether, 63.0 mL, 189.0 mmol) dropwise. The reaction was stirred below −40° C. for 18 h, and the reaction was slowly warmed to 0° C. and quenched with 50% saturated aqueous ammonium chloride solution (100 mL). The phases were separated, and the organic layer was washed with deionized water (50 mL). The aqueous layer was further extracted with ethyl acetate (2×50 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude material was purified by flash chromatography (SiO2, 50% ethyl acetate in hexanes) to afford the desired product (14.6 g, 44.5 mmol, 52%). quenched with 50% saturated aqueous ammonium chloride solution (100 mL) The phases were separated the organic layer was washed with deionized water (50 mL) The aqueous layer was further extracted with ethyl acetate (2×50 mL) The combined organic layers were dried (Na2SO4) filtered concentrated in vacuo The crude material was purified by flash chromatography (SiO2, 50% ethyl acetate in hexanes)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of the crude (S)-N-(4-chloro-2-(trifluoromethyl)benzylidene)-2-methylpropane-2-sulfinamide (26.8 g, 86.0 mmol) in dichloromethane (290 mL) at −48° C. was added a solution of methyl magnesium bromide (3.0 M in diethyl ether, 63.0 mL, 189.0 mmol) dropwise. The reaction was stirred below −40° C. for 18 h, and the reaction was slowly warmed to 0° C. and quenched with 50% saturated aqueous ammonium chloride solution (100 mL). The phases were separated, and the organic layer was washed with deionized water (50 mL). The aqueous layer was further extracted with ethyl acetate (2×50 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude material was purified by flash chromatography (SiO2, 50% ethyl acetate in hexanes) to afford the desired product (14.6 g, 44.5 mmol, 52%). quenched with 50% saturated aqueous ammonium chloride solution (100 mL) The phases were separated the organic layer was washed with deionized water (50 mL) The aqueous layer was further extracted with ethyl acetate (2×50 mL) The combined organic layers were dried (Na2SO4) filtered concentrated in vacuo The crude material was purified by flash chromatography (SiO2, 50% ethyl acetate in hexanes)

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

Procedure: To a solution of (S)—N—((R)-1(4-chloro-2-(trifluoromethyl)phenyl)ethyl)-2-methylpropane-2-sulfinamide (14.6 g, 44.5 mmol) in methanol (25 mL) was added a solution of hydrochloric acid in p-dioxane (4.0 M in p-dioxane, 22.3 mL, 89.1 mmol), and the reaction was stirred at room temperature for 30 min. Diethyl ether was then added (400 mL) and the slurry was stirred for 10 min. The solid was collected by filtration, and washed with diethyl ether (2×200 mL). The solid was then dissolved in 5 M aqueous sodium hydroxide solution, and extracted with dichloromethane (2×100 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was used without further purification (7.8 g, 34.9 mmol, 79%, >96% ee, determined by Mosher's method). the slurry was stirred for 10 min The solid was collected by filtration washed with diethyl ether (2×200 mL) The solid was then dissolved in 5 M aqueous sodium hydroxide solution extracted with dichloromethane (2×100 mL) The combined organic layers were dried (Na2SO4) filtered concentrated in vacuo The crude product was used without further purification (7.8 g, 34.9 mmol, 79%, >96% ee, determined by Mosher's method)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of the crude (S)—N-(4-chloro-2-(trifluoromethyl)benzylidene)-2-methylpropane-2-sulfinamide (26.8 g, 86.0 mmol) in dichloromethane (290 mL) at −48° C. was added a solution of methyl magnesium bromide (3.0 M in diethyl ether, 63.0 mL, 189.0 mmol) dropwise. The reaction was stirred below −40° C. for 18 h, and the reaction was slowly warmed to 0° C. and quenched with 50% saturated aqueous ammonium chloride solution (100 mL). The phases were separated, and the organic layer was washed with deionized water (50 mL). The aqueous layer was further extracted with ethyl acetate (2×50 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude material was purified by flash chromatography (SiO2, 50% ethyl acetate in hexanes) to afford the desired product (14.6 g, 44.5 mmol, 52%). quenched with 50% saturated aqueous ammonium chloride solution (100 mL) The phases were separated the organic layer was washed with deionized water (50 mL) The aqueous layer was further extracted with ethyl acetate (2×50 mL) The combined organic layers were dried (Na2SO4) filtered concentrated in vacuo The crude material was purified by flash chromatography (SiO2, 50% ethyl acetate in hexanes)