2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → tert-butyl (2-chloro-4-{2-[(1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl]ethoxy}phenyl)acetate

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(4-{(1R,2S)-2-[2-(4-bromo-3-chlorophenoxy)ethyl]cyclopropyl}piperidin-1-yl)-5-(methoxymethyl)pyrimidine (0.91 g, 1.89 mmol) in THF (10 ml) was added 2-tert-butoxy-2-oxoethylzinc chloride (9.46 ml, 4.73 mmol). Nitrogen gas bubbled through the mixture for 10 min. then Pd2(dba)3 (0.087 g, 0.189 mmol) and X-PHOS (0.090 g, 0.189 mmol) were added and the resulting mixture heated at 60° C. for 30 min. The mixture was cooled, diluted with ethyl acetate (20 mL), washed with aqueous ammonium chloride (saturated, 1×15 mL), dried over MgSO4, filtered and the solvent evaporated under reduced pressure. The residue was purified by column chromatography on silica gel Biotage 50M, using a gradient eluant of EtOAc/Hexane (0-50%) to afford the title compound. LC/MS (m/z): 516 (M+H)+.

Provenance & Evidence