Efficient and Industrially Viable Synthesis of Donepezil

Abstract

An efficient, economically viable process has been developed for large‐scale preparation of donepezil HCl (1), an anti‐Alzheimer's agent. The process involves the condensation of 5,6‐dimethoxy‐1‐indanone (3) and 1‐benzyl‐4‐piperidinecarboxaldehyde (4) in the presence of alkalimetal carbonates at elevated temperature to yield 1‐benzyl‐4‐[(5,6‐dimethoxy‐1‐indanone)‐2‐yidenyl] methyl piperidine (2), the key intermediate in the synthesis of donepezil. Hydrogenation of 2 yields donepezil.

Keywords:

• anti‐Alzheimer's agent
• aqueous alkali metal carbonates
• condensation
• donepezil
• economically viable

Acknowledgment

The authors thank the management of Natco Pharma Ltd. for supporting this work. The technical service from the analytical division of Natco Research Centre is gratefully acknowledged.