Improved One-Pot Synthesis of Citalopram Diol and Its Conversion to Citalopram

An improved process is developed for the preparation of citalopram diol, 2 which involves two consecutive Grignard reactions in situ followed by an efficient and simple workup process with improved overall yield. Process development efforts for conversion of 2 into citalopram, 1, and a control strategy for impurities are discussed. The present work addresses the challenges associated with the process development and scale-up of citalopram such as handling of unstable intermediates, control of various potential impurities, and process safety to achieve an economic and scalable process.