Phosphate → 2-(R)-[2-(S)-Benzyl-1-(S)-hydroxy-3-(4-(S)-isopropyl-2-oxo-oxazolidin-3-yl)-3-oxopropyl]-4-(R)-fluoropyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

Add dibutylboron triflate (1 M in dichloromethane, 11.8 mL, 11.8 mmol) to a solution of 4-(S)-isopropyl-3-(3-phenylpropionyl)-oxazolidin-2-one (2.8 g, 10.7 mmol) in dichloromethane (40 mL) at 0° C. Stir 5 min. Add N,N-diisopropylethylamine (2.25 mL, 12.87 mmol) and stir 90 min. Cool to −78° C. and add 4-(R)-fluoro-2-(R)-formylpyrrolidine-1-carboxylic acid tert-butyl ester (2.53 g, 11.6 mmol) in dichloromethane (15 mL) over 15 min. Stir 90 min and then warm to room temperature over 18 h. Cool in ice bath and add 0.05 M pH 7 phosphate buffer (15 mL). Extract with dichloromethane and concentrate. Dissolve in methanol (50 mL) and cool in ice bath. Add aqueous hydrogen peroxide (15 mL, 30% solution) and remove ice bath. Stir 5 min and concentrate. Extract with ethyl acetate and wash extract with 1 N HCl, saturated aqueous sodium bicarbonate, saturated aqueous sodium chloride, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with hexanes and ethyl acetate) to give the title compound as a foam (2.68 g, 52%).

Provenance & Evidence