Resolution of racemic cis-1-amino-2-indanol by diastereomeric salt formation with ( S)-2-phenylpropionic acid

Abstract

Resolution of racemic cis-1-amino-2-indanol 1, a key intermediate for the synthesis of indinavir, is reported. The conditions were optimized for an industrial-scale resolution of racemic cis- 1 using ( S)-2-phenylpropionic acid 6 as the resolving agent and ethanol as the solvent. The less-soluble diastereomeric salt, (1 R,2 S)- 1·( S)- 6, was obtained in 35% yield with 99% de ( E >69%) by crystallization. Resolving agent 6 was efficiently recovered from the salt and the mother liquor.