Hydrochloric Acid → (4S,5R)-5-[3-fluoro-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

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Reaction Steps

Lithium tri-tert-butoxyaluminohydride (18.27 ml, 74.0 mmol) was added into a cold (dry ice/acetone bath) solution of benzyl {(2S)-1-[3-fluoro-5-(trifluoromethyl)phenyl]-1-oxopropan-2-yl}carbamate (5.4655 g, 14.80 mmol) in ethanol (100 ml). LCMS indicated the reaction was completed in 10 min. The reaction was quenched by HCl (1N). The crude mixture was diluted with ethyl acetate and filtered through a bed of Celite® 521 (slow filtration). Volatiles were removed from the filtrate under reduced pressure. The resulting pot residue was worked up with aqueous sodium hydrogen carbonate/brine, extracted with ethyl acetate, dried over Na2SO4, filtered and evaporated to afford a white solid. This solid was stirred with potassium hydroxide (10 ml, 75 mmol) in a THF (100 ml)/methanol (50 ml) mixture at room temp for 2 hrs. LCMS indicated completion of reaction. HCl (1N) was added to acidify the reaction mixture. Volatiles were removed under reduced pressure. The pot residue was worked up with brine, extracted with ethyl acetate, dried over Na2SO4, filtered and evaporated to afford a dark mixture. The resulting mixture was purified by flash chromatography (SiO2, Biotage 65i cartridge). The column was eluted by an ethyl acetate/hexanes mixture (0% to 100% ethyl acetate). Related fractions were pooled and evaporated under reduced pressure to afford a white solid of 2.6765 g as the titled compound. LCMS calc.=263.06. found=262.11 (M−1)−. 1H-NMR (CDCl3, 500 MHz) δ 7.36 (s, 1H), 7.34 (d, J=8.5 Hz, 1H), 7.27 (d, J=9 Hz, 1H), 5.8 (d, J=7.5 Hz, 2H), 4.3 (ps quintet, J=6.9 Hz, 1H), 0.85 (d, J=6.5 Hz, 3H).

Provenance & Evidence