Overcoming a solid solution system on chiral resolution: combining crystallization and enantioselective dissolution

Abstract

Chiral resolution of rac-4-cyano-1-aminoindane, a key intermediate of ozanimod, was successfully achieved through a combination of crystallization and enantioselective dissolution with up to 96% ee. The disastereomeric salt with di-p-toluoyl-l-tartaric acid was characterized by the construction of a binary phase diagram and ternary isotherm. Enantioselective dissolution was then employed to further enrich the enantiomer.