Resolution of Racemic Mixtures by Phase Transition of PEGylated Resolving Agents

Abstract

A novel, efficient, and simple method for the resolution of racemic mixtures is presented in which PEGylated resolving agents are subjected to diastereomeric complex formation in alcohols. The resulting complexes then undergo temperature-assisted phase transition, affording a precipitate that is enriched in one enantiomer and separable by filtration. In an aqueous solution, phase transition can be caused by the methods used in the precipitation of poly(ethylene glycol) (e.g., addition of ammonium sulfate). A number of racemic amines have been successfully resolved using this method. The first cycle of resolution affords the amines with an optical purity of 72-85% from their corresponding racemic mixture in good yields (78-90%). An additional cycle improved the optical purity to 87-95%. The PEGylated resolving agents can be recovered and reutilized without the loss of resolution efficiency.