Ethyl Acetate → (5R,5'R)-4,4'-Bis-(5-(1H-1,2,3-triazol-1-yl)methyl-2-oxo-oxazolidin-3-yl)-2,2'-difluoro-biphenyl

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of (5R)-3-(3-fluoro-4-(trimethylstannyl)phenyl)-5-(1H-1,2,3-triazol-1-ylmethyl)-1,3-oxazolidin-2-one (425 mg, 1.0 mmol), 2-bromo-5-cyano-thiazole (189 mg, 1.0 mmol, and copper(I) iodide in dimethylformamide (5 ml) was purged with a slow stream of nitrogen for 20 min and then tetrakis(triphenylphosphine)palladium(0) (58 mg, 0.05 mmol) was added. The stirred reaction mixture was maintained at 70° C. under an atmosphere of nitrogen for 5 hours. The stirred reaction mixture was treated with aqueous potassium fluoride (10%, 20 ml) and then stirred for 30 min, treated with ethyl acetate (20 ml). The precipitate was isolated by filtration to give fraction A of impure product. The organic phase was separated, dried (MgSO4), treated with silica-gel (500 mg), and evaporated under reduced pressure to leave a free-running solid. The solid was applied to a silica-gel column and eluted with dichloromethane-methanol (0%-10% methanol gradient) to give a further fraction B of impure product. Fractions A and B were dissolved in DMSO (6 ml total), combined, and purified by reverse phase hplc to give the desired product (18 mg).

Provenance & Evidence