Development of a manufacturing process for zatosetron maleate

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.