A new commercially viable synthetic route for donepezil hydrochloride: anti-Alzheimer's drug

Chem Pharm Bull (Tokyo). 2010 Sep;58(9):1157-60. doi: 10.1248/cpb.58.1157.

Abstract

An economical new process has been developed for the synthesis of donepezil hydrochloride (1) an anti-Alzheimer's drug. The process involves Darzen reaction of pyridine-4-carboxaldehyde and 2-bromo-5,6-dimethoxy indanone affording epoxide 5,6-dimethoxy-3-(pyridine-4-yl)spiro[indene-2,2'-oxiran]-1(3H)-one (4) as a key intermediate. The one-pot deoxygenation of 4 and hydrogenation of the aryl moiety in high yield improved the overall yield of the process.

MeSH terms

  • Alzheimer Disease / drug therapy
  • Donepezil
  • Humans
  • Indans / chemical synthesis*
  • Nootropic Agents / chemical synthesis*
  • Piperidines / chemical synthesis*
  • Technology, Pharmaceutical / economics
  • Technology, Pharmaceutical / methods*

Substances

  • Indans
  • Nootropic Agents
  • Piperidines
  • Donepezil