Characterization of a conglomerate-forming derivative of (±)-milnacipran and its enantiomeric resolution by preferential crystallization

Abstract

Among some derivatives of milnacipran, a last-generation antidepressive drug with useful application in the treatment of fibromyalgia, N-isobutyramide (±)-4 was identified as a conglomerate-forming compound and characterized using a binary melting diagram and X-ray analysis. Exploiting the conglomerate nature of (±)-4, its enantiomeric resolution by preferential crystallization was shown to be feasible and allowed us to obtain both enantiomers in satisfactory yield and excellent optical purity over a few cycles of entrainment.