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Efficient and Industrially Viable Synthesis of Donepezil
Authors:R Janaki Rama Rao  Y L N Murthy
Institution:1. Natco Research Centre, Natco Pharma Limited , Hyderabad, Andhra Pradesh, India;2. Department of Organic Chemistry , Andhra University , Visakhapatnam, Andhra Pradesh, India
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
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