Resolution of Omeprazole Using Coupled Preferential Crystallization: Efficient Separation of a Nonracemizable Conglomerate Salt under Near-Equilibrium Conditions

A facile and efficient resolution of omeprazole as the monopotassium salt diethanol solvate using coupled preferential crystallization has been developed. This approach uses small perturbations in solution-phase concentration to control the competing process of selective crystal growth while suppressing unwanted primary nucleation. The result is a selective crystallization technique that replaces the traditional batch-type isolation with a continuous process amenable to scale, which provides easy access to enantiopure conglomerate crystals.