Improved Syntheses of N‐Desmethylcitalopram and N,N‐Didesmethylcitalopram

Abstract

An improved and efficient synthesis of N‐desmethylcitalopram (2) and N,N‐didesmethylcitalopram (3) is presented. The method involved N‐demethylation of citalopram (1) using 1‐chloroethyl chloroformate to give 2 in 87% yield. Synthesis of 3 was accomplished by alkylation of 8 with 1‐(3‐bromopropyl)‐2,2,5,5‐tetramethyl‐1‐aza‐2,5‐disilacyclopentane (9).

Keywords:

• citalopram
• N‐desmethylcitalopram
• N,N‐didesmethylcitalopram
• N‐demethylation

Acknowledgment

This work was supported by the National Institute of Mental Health under Contract N01‐MH‐32005. We thank James Windak, Chemistry Department, University of Michigan, Ann Arbor, Michigan, for the high‐resolution mass spectral analyses.