Chlorotrimethylsilane → Racemic (5-chloropyridin-2-yl)(cyclohexyl)(3-fluoro-5-(trifluoromethyl)phenyl)methanamine

Participants

Reaction Conditions

Reaction Steps

A dry 200 mL flask under nitrogen was charged with 1-bromo-3-fluoro-5-(trifluoromethyl)benzene (1.22 g, 0.005 mol). Dry ether (50mL) was added and the solution was cooled to −78° C. n-BuLi (3.0 mL, 1.6 M in hexanes, 0.0048 mol) was added dropwise and the resulting solution was stirred at −78° C. for 30 min. A solution of 5-chloropicolinonitrile (0.692 g, 0.005 mol) in anhydrous THF (7 mL) was then added. The resulting solution was stirred at −78° C. for 1 hr. Redistilled TMSCl (0.65 mL, 0.00515 mol) was added dropwise. The reaction mixture was allowed to reach 0° C. and then cooled to −78° C. Cyclohexylmagnesium chloride (2.75 mL, 2.0 M, 0.0055 mol) was added dropwise. The solution was allowed to reach room temperature. The reaction was quenched by addition of water followed by aqueous ammonium chloride. The aqueous layer was extracted with ether (2×50 mL). The combined organic portions were filtered through a pad of silica and the silica was washed with 4:1 Hexanes:EtOAc. The solvents were evaporated to get the racemic (5 -chloropyridin-2-yl)(cyclohexyl)(3-fluoro-5-(trifluoromethyl)phenyl)methanamine as an oil (1.39 g, 75% yield). LCMS RT=3.28 min, [M+H] 387.14, Purity 79% (LCMS Method 6).

Provenance & Evidence