Sodium hydride → (4S,5R)-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-5-[3-fluoro-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

Participants

Reaction Steps

To a cold (ice/methanol bath) mixture of (4S,5R)-5-[3-fluoro-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 93) (5000 mg, 19.00 mmol) in THF (100 ml) was added sodium hydride (912 mg, 22.80 mmol) all at once. The resulting mixture was stirred cold (ice bath) for 1.5 hrs followed by addition of 3-bromo-2-(bromomethyl)-6-chloropyridine (INTERMEDIATE 30) (5963 mg, 20.90 mmol). The reaction mixture was allowed to slowly warm to ambient in 3 hrs. The reaction was cooled (ice bath) and quenched by HCl (1N, aq.). The resulting mixture was extracted with ethyl acetate, dried over Na2SO4, filtered and evaporated under reduced pressure to afford an oil. This oil was purified by flash chromatography (SiO2, Biotage 65i cartridge). The column was eluted by an ethyl acetate/hexanes mixture (0% to 40% ethyl acetate). Related fractions were pooled and concentrated in vacuo to afford a light amber gum of 8.2522 g as the titled compound. LCMS calc.=465.97. found=468.91.

Provenance & Evidence