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

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Reaction Conditions

Reaction Steps

To CuF(PPh3)3 methanol solvate (0.137 g) and (RP)-1-[(R)-α-(dimethylamino)-2-(diphenylphosphino)benzyl]-2-diphenylphosphinoferrocene (0.100 g) was added tetrahydrofuran (14 mL). The mixture was stirred at 0-5° C. (under argon) for 30 minutes until all solids were dissolved. To this solution was then added phenyl silane (0.789 g). After 10 minutes, a solution of 5-fluoro-4-vinylpyrimidine (0.903 g) and 2-chloro-1-(2,4-difluorophenyl)ethanone (1.68 g) in tetrahydrofuran (22 mL) was added over 30 minutes. The reaction mixture was stirred for 1 hour at 0-5° C. after which no further 5-fluoro-4-vinylpyrimidine was observable by HPLC. The reaction was quenched by addition of aqueous ammonium chloride (1 M, 15 mL), followed by methyl tert-butyl ether (30 mL). The organic layer was dried to a residue which was then subjected to purification by column chromatography (eluting with 5-40% ethyl acetate in cyclohexane) to give (2R,3S)-1-chloro-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)butan-2-ol as a white solid (1.70 g, 74% yield).

Provenance & Evidence