New Technical Synthesis of Ethyl (R)-2-Hydroxy-4-phenylbutyrate of High Enantiomeric Purity

A new technical synthesis to produce ethyl (R)-2-hydroxy-4-phenylbutyrate (5), an important intermediate for several ACE inhibitors with >99% ee in an over-all yield of 50–60% is described starting from acetophenone and diethyl oxalate. Key step is the chemo- and enantioselective hydrogenation of ethyl 2,4-dioxo-4-phenylbutyrate (6) (ee up to 86%) catalyzed by a heterogeneous Pt catalyst modified with dihydrocinchonidine, followed by crystallization of the 2-hydroxy-4-oxo ester 7 and hydrogenolysis of the 4-keto group.