Transformation of racemic ethyl 3-hydroxybutanoate into the ( R)-enantiomer exploiting lipase catalysis and inversion of configuration

Abstract

Racemic ethyl 3-hydroxybutanoate rac- 1 was transformed into ethyl ( R)-acetoxybutanoate (ee = 92%) with 85–90% chemical yields using enantioselective acylation with isopropenyl acetate in the presence of Candida antarctica lipase B (CAL-B, Novozym 435) under solvent-free conditions, followed by mesylation of the unreacted ( S)-alcohol in the reaction mixture and inversion of configuration with cesium acetate in DMF in one pot. When the ( R)-acetoxybutanoate was subjected to alcoholysis with ethanol and CAL-B, enantiopure ( R)- 1 (ee >99%) was produced.