Sodium Bicarbonate → 1-((4S,5R)-5-(4-(6-(3-aminooxetan-3-yl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-2,2-dimethyloxazolidin-3-yl)-2,2-difluoroethanone

Participants

Reaction Conditions

Reaction Steps

To a toluene/ethanol (15 ml toluene, 12 ml ethanol) solution of 2,2-difluoro-1-((4S,5R)-4-(fluoromethyl)-2,2-dimethyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidin-3-yl)ethanone (594 mg, 1.44 mmol) is added 3-(5-bromopyridin-2-yl)oxetan-3-aminium chloride (434 mg, 1.44 mmols), sodium bicarbonate (3 mL of a 2M solution) and Pd(dppf)2Cl2 (150 mg, 0.2 mmol)). The reaction mixture is heated to 80° C. while stirring under nitrogen for two hours. The reaction is cooled to room temperature and diluted with ethyl acetate (60 ml). The mixture is washed water (2×10 ml). The organic phase is dried over sodium sulfate and concentrated. The residual material is purified on silica gel (mobile phase 6% methanol in methylene chloride) to give the title compound (436 mg, 70%): m/z (Cl) 436 [M+H]+.

Provenance & Evidence