Donepezil → 5,6 Dimethoxy-2-(pyridin-4yl)-methylene-indan-1one

Participants

Reaction Steps

In a preferred embodiment, the present invention relates to an improved and convenient process for the preparation of 2,3-dihydro-5,6-dimethoxy-2[[1-(phenyl methyl)-4-piperidinyl]methyl]-1H-inden-1-one (Donepezil) of the formula (I), which involves a reaction of 5,6-dimethoxy indanone of the formula (II) with pyridine-4-carboxaldehyde of the formula (III) in the presence of an organic solvent to afford 5,6 dimethoxy-2-(pyridin-4-yl)-methylene indan-1-one of the formula (IV). The compound of the formula (IV) is hydrogenated under palladium carbon catalyst in the presence of acetic acid in methanol to afford the acetate salt of the formula (V), which is in situ converted to the key intermediate 5,6-dimethoxy-2-piperidin-4-yl-methyl indan-1-one of the formula (VI). Further reaction of the formula (VI) with benzyl bromide in a solvent in the presence of base yields donepezil of the formula (I) in an overall yield of 83%. The relevant synthetic scheme may be schematically depicted as follows:

Provenance & Evidence