Novel Process for Production of Highly Pure Polymorph (I) Donepezil Hydrochloride

A process for the preparation of highly pure Polymorph (I) donepezil hydrochloride of Formula I with

• hydrogenating of 5,6-dimethoxy-2-(pyridine-4-ylmethylene)indane-1-one salt intermediate of Formula IV, and subsequent
• benzylating of the obtained 4-[(5,6-dimethoxy-1-indanon)-2-yl]-methyl piperidine intermediate of Formula V, and subsequent
• salt-forming steps with reacting donepezil base of Formula VI, and subsequent re-crystallizing of the obtained donepezil hydrochloride of Formula I from a solution containing a short carbon chain alcohol,
• which process comprises:
• a. accomplishing the said hydrogenating of 5,6-dimethoxy-2-(pyridine-4-yl methylene)indan-1-one hydrochloride of Formula IV in the presence of charcoal Pd catalyst, and
• b. accomplishing the said salt-forming steps with reacting donepezil base of Formula VI by acidic acid, then extracting the acetic acidic salt into aqueous phase, then transforming it again to donepezil base in the presence of a base, then transforming the latter into donepezil hydrochloride of Formula I in the presence of hydrogen chloride, and
• c. accomplishing the said re-crystallizing with precipitating the Polymorph (I) donepezil hydrochloride product from aqueous alcoholic solution containing 2-18% water.