Zatosetron maleate is a potent, selective 5-hydroxytryptamine receptor antagonist. In anticipation of commercialization, a manufacturing synthesis of zatosetron from tropinone and 5-chlorosalicylic acid was developed. Development efforts focused on addressing several key issues including the supply and quality of the critical raw material tropinone, improvements in the stereoselective formation of 3-endo-tropanamine, and the compatibility with existing manufacturing capabilities of process requirements for the Claisen rearrangement used to produce a crucial benzofuran intermediate. The results of these studies and an improved route to zatosetron maleate are described.

Development of a Manufacturing Process for Zatosetron Maleate. -An efficient route for the commercial-scale synthesis of the title compound (X)· maleate, a potent 5-hydroxytryptamine receptor antagonist, is presented. -(BURKS, J. E. JUN.; ESPINOSA, L.; LABELL, E. S.; MCGILL, J. M.; RITTER, A. R.; SPEAKMAN, J. L.; WILLIAMS, M.; BRADLEY, D. A.; HAEHL, M. G.; SCHMID, C. R.; Org. Process Res. Dev. 1 (1997) 3, 198-210; Chem. Process Dev., Tippecanoe Lab., A Div. Eli Lilly Co., Lafayette, IN 47902, USA; EN)