Hydrochloric Acid → Donepezil Hydrochloride

Participants

Reaction Conditions

Reaction Steps

50 g of donepezil was dissolved by stirring in 320 g (400 ml) of ethanol under heating, followed by adding 15.1 g of concentrated hydrochloric acid thereto at the internal temperature of 30° C. Then, it was cooled and continued stirring while keeping the internal temperature at about 20° C. Crystals started precipitating about 30 minutes after the concentrated hydrochloric acid was poured into the mixture. After the precipitation started, the mixture was stirred at the internal temperature of 20° C. for 18 hours and then cooled to the internal temperature of 9° C. The crystals were collected by filtration and dried about 5 hours and a half after the cooling was started, to give 52.3 g of polymorphic crystal (III) of donepezil hydrochloride (yield: 95.4%).

Provenance & Evidence