Study On The Synthesis Of Donepezil Hydrochloride

Donepezil Hydrochloride, named l-benzyl-4-[(5,6-dimethoxy-l-indanon)-2-yl]methyl pyridine hydrochloride, was the second generation reversibility anticholinesterase inhibitor and the second medicament for treating Alzheime disease(AD) authorized by FDA.By comparison of the merits and demerits of the processes for the preparation of Donepezil Hydrochloride, on the objective of being friendly to environment, employing cheaper and easily available raw materials, employing less number of reaction steps and consuming less time, being convenient and safe to carry out, giving high yield and purity of products, and being suitable for industrial scale up, the route invented by Bayer company was adopted as the experiment route of this paper, and some of its operation conditions were modified on the basis of other document. In this paper, Donepezil Hydrochloride was synthesized from 5,6-dimethoxyindanone and pyridine-4-aldehyde via Condensation reaction, phenmethyl research, hydrogenation and acidification research. During the experiment, we paid attention to the following reaction conditions which affect the reaction yield such as reaction time, reaction temperature, the molar ratio reactant the dosage of catalyst and so on .by means of orthogonal design method, optimum reactant composition and reaction conditions were obtained, the dynamics process of phenmethyl research was further discussed and the dynamics equation was established.The synthesized products were confirmed by m.p , IR ~1HNMR and else analysis to be consistent with the target product.