Hydrochloric Acid → Donepezil Hydrochloride

Participants

Reaction Conditions

Reaction Steps

50 g of donepezil was dissolved by stirring in 320 g of ethanol under heating, followed by adding 15.1 g of concentrated hydrochloric acid thereto at the internal temperature of 30° C. After concentrated hydrochloric acid was poured, 100 mg of seed crystals were added. The mixture was cooled and continued stirring while keeping the internal temperature at about 20° C. Crystals started precipitating immediately after the seed crystals were added. 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 3 hours after the cooling was started, to give 52.90 g of polymorphic crystal (III) of donepezil hydrochloride (yield: 96.5%).

Provenance & Evidence