Sodium Bicarbonate → 2-Propanol, 2-methyl-, lithium salt (1:1)

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Reaction Conditions

Reaction Steps

A solution of lithium tert-butoxide was prepared by addition of n-butyllithium (1.6 m in hexane, 2.9 ml) to a stirred solution of tert-butanol (0.43 g) in anhydrous THF (10 ml) at -10° C. under argon. After cooling to -70° C., a solution of 5-benzyloxycarbonylamino-2-(4-{2-fluoroethyl}-3-oxopiperazin-1-yl)fluorobenzene (1.5 g) in dry THF (15 ml) was added. After 10 minutes, (R)-glycidylbutyrate (0.67 g) in dry THF (15 ml) was added to the resulting mixture, and stirring continued at -70° C. for 15 minutes, before allowing the temperature to rise to ambient over 16 hours. Methanol (10 ml) was added, followed by saturated sodium bicarbonate solution (20 ml) and water (10 ml). The organics were extracted into ethyl acetate (3×25 ml), washed with brine and dried (MgSO4). Solvent was evaporated and the residue purified by chromatography on silica, using as eluant a gradient increasing in polarity from 0 to 3% methanol in dichloromethane. Relevant fractions were combined and evaporated to give (5R)-3-(3-fluoro-4-{4-(2-fluoroethyl)-3-oxopiperazin-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one (1.07 g).

Provenance & Evidence