Optical resolution by preferential crystallization of 4‐methylpiperidinium hydrogen (RS)‐phenylsuccinate

Abstract

AbstractGibbs energy of racemate formation, binary melting point diagram, and ternary solubility diagram suggested that 4‐piperidinium hydrogen (RS)‐phenylsuccinate [(RS)‐4‐MP salt] exists in a conglomerate. Appropriate conditions were explored on the basis of free energy of critical nucleation in a supersaturated solution to resolve efficiently (RS)‐4‐MP salt by preferential crystallization. Successive preferential crystallization of (RS)‐4‐MP salt in ethanol at 20°C gave (R)‐ and (S)‐4‐MP salts of 90–94% optical purities. Optically pure (R)‐ and (S)‐phenylsuccinic acids were obtained by recrystallization of the (R)‐ and (S)‐4‐MP salts, followed by treatment of the salts purified with hydrochloric acid. © 1994 Wiley‐Liss, Inc.