Improved Synthesis and Impurity Control Strategy of Penehyclidine Hydrochloride

A scalable process for the synthesis of high-purity penehyclidine hydrochloride (99.9% by HPLC area %) without purification by fractional distillation has been developed with significantly improved overall yield, where a robust and cost-effective Corey–Chaykovsky reaction was successfully explored. Critical parameters of each step and process-related impurities were identified, and all impurities reported in this work have been independently synthesized, which could promote the understanding of the impurity profile and potentially boost the upgrade of the drug standard.