Chirality switching in the enantioseparation of 2-hydroxy-4-phenylbutyric acid: Role of solvents in selective crystallization of the diastereomeric salt

Abstract

Chirality switching was induced by solvents in the enantioseparation of 2-hydroxy-4-phenylbutyric acid (HPBA) via diastereomeric salt formation with an enantiopure aminoalcohol. The (S)-salt was crystallized from butanol solutions and the (R)-salt was obtained from aqueous solutions. It was found from crystallographic analysis of the salts that solvent inclusion changed the solubility of both salts. In particular, the (R)-salt afforded multiple pseudo-polymorphic hydrated crystals. Successive crystallization from two different solvents efficiently afforded both pure diastereomeric salts.