Conversion of L-Pyroglutamic Acid to 4-Alkyl-Substituted L-Prolines. The Synthesis of trans-4-Cyclohexyl-L-proline

Article abstract of DOI:10.1021/jo00366a011

(S)-5-(Hydroxymethyl)-2-pyrrolidinone (3), prepared from L-pyroglutamic acid, was condensed with benzaldehyde to obtain the O,N-acetal 4 in excellent yield.Alkylation of 4 with 3-bromocyclohexene followed by reduction gave trans-4-cyclohexyl-L-prolinol (7) in good chemical yield with excellent stereoselectivity.Sequential N-protection, oxidation of the alcohol to the acid, and N-deprotection furnished trans-4-cyclohexyl-L-proline (1) in excellent yield and quality.Compound 1 serves as an intermediate for the preparation of ACE inhibitors including Fosenopril.