Phenylsilane → (2R,3S)-1-chloro-3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)butan-2-ol

Participants

Reaction Conditions

Reaction Steps

To CuF(PPh3)3 methanol solvate (0.0094 g) and (RP)-1-[(R)-α-(dimethylamino)-2-(diphenylphosphino)benzyl]-2-diphenylphosphinoferrocene (0.0068 g) under argon was added tetrahydrofuran (1 mL). The mixture was stirred at 20° C. (under argon) for 30 minutes until all solids were dissolved. The solution was then cooled to −20° C. and phenyl silane (0.027 g) was added. After 10 minutes, a solution of 4-chloro-5-fluoro-6-vinylpyrimidine (0.180 g) and 2-chloro-1-(2,4-difluorophenyl)ethanone (0.095 g) in tetrahydrofuran (1.5 mL) was added over approximately 5 minutes. The reaction mixture was stirred for 1 hour at −20° C. until complete consumption of the vinyl pyrimidine was observed by HPLC analysis. The reaction was quenched by addition of aqueous ammonium chloride (1 M, 3 mL), followed by methyl tert-butyl ether (5 mL). The organic layer was dried to a residue which was then subjected to purification by column chromatography (eluting with 0-20% ethyl acetate in cyclohexane) to give (2R,3S)-1-chloro-3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)butan-2-ol (0.259 g, 65% yield) as a white solid.

Provenance & Evidence