Practical continuous resolution of α-amino-ε-caprolactam by diastereomeric salt formation using a single resolving agent with a solvent switch method

Abstract

A practical procedure for the continuous resolution of ( R)-(+)- and ( S)-(−)-α-amino-ε-caprolactams 1 from the racemate by diastereomeric salt formation has been developed using a single naturally-based resolving agent, N-tosyl-( S)-phenylalanine 5, together with a simple solvent switch method. The ( S)- 1·( S)- 5·H 2O salt (30%, 93% de, E 56%) was obtained by crystallization from MeOH, while the ( R)- 1·( S)- 5 salt (41%, 92% de, E 75%) was crystallized from the 2-propanol: water (89:11) of the condensate of the mother liquor after the first crystallization. The ( R)- 1 hydrochloride was efficiently prepared from the crude salt without further purification with high enantiomeric purity in >99.9% ee and 36% yield versus ( RS)- 1.