Simple Two-step Procedure for the Synthesis of Memantine Hydrochloride from 1,3-Dimethyl-adamantane

Binh Duong Vu; Ngoc Minh Ho Ba; Van Hien Pham; Dinh Chau Phan

doi:10.1021/acsomega.0c01589

Simple Two-step Procedure for the Synthesis of Memantine Hydrochloride from 1,3-Dimethyl-adamantane

ACS Omega. 2020 Jun 25;5(26):16085-16088. doi: 10.1021/acsomega.0c01589. eCollection 2020 Jul 7.

Authors

Binh Duong Vu¹, Ngoc Minh Ho Ba¹, Van Hien Pham¹, Dinh Chau Phan²

Affiliations

¹ The Drug R&D Center, Vietnam Military Medical University, No. 160, Phunghung Street, Phuc La Ward, Hadong District, Hanoi 12108, Vietnam.
² School of Chemical Engineering, Hanoi University of Science and Technology, No. l, Daicoviet Street, Bach Khoa Ward, Haibatrung District, Hanoi 11600, Vietnam.

Abstract

Memantine hydrochloride is a medicine used for the treatment of Alzheimer's disease. A number of methods for the preparation of memantine hydrochloride have been reported. These procedures started from 1,3-dimethyl-adamantane by as many as using three or four reaction steps to produce memantine hydrochloride with overall yields ranging from 54 to 77%. In this article, a simple, concise two-step synthesis of memantine hydrochloride from 1,3-dimethyl-adamantane via N-formamido-3,5-dimethyl-adamantane with an improved overall yield of 83% was developed. In step 1, 3,5-dimethyl-adamantane was reacted with formamide and nitric acid to afford 1-formamido-3,5-dimethyl-adamantane in 98% yield, followed by hydrolysis of 1-formamido-3,5-dimethyl-adamantane with aq hydrochloride to give memantine hydrochloride in 85% yield. The procedure can be easily deployed at an industrial scale.