Two Step Cost-Saving Process for Industrial Scale Production of 1-Amino-3,5-dimethyladamantane Hydrochloride (An Anti-Alzheimer’s Drug)

Thi Hong Tham Nguyen1,, Viet Duc Le2,, Sy Thinh Ngo3,, Thi Hong Thanh Nguyen4,, Dinh Chau Phan5, and Binh Duong Vu1,*,

1Vietnam Military Medical University, No. 160, Phung Hung Str., Phuc La Ward, Ha Dong District, Hanoi 100000, Vietnam

2Military Institute of Drug, Medical Equipment Quality Control and Research, Km 15, Lien Ninh Ward, Thanh Tri District, Hanoi, Vietnam

3354 Military Hospital, 120 Doc Ngu, Ba Dinh, Hanoi, Vietnam

4Vinh Medical University, 161 Nguyen Phong Sac, Vinh, Nghe An, Vietnam

5School of Chemical Engineering, Hanoi University of Science and Technology, No.1, Dai Co Viet Str., Bach Khoa Ward, Hai Ba Trung District, Hanoi, Vietnam

*Corresponding author: Tel: +84 983425460; E-mail:


This work presents a predominant cost-saving process for the industrial scale synthesis of memantine hydrochloride (1) from 1,3-dimethyladamantane (2) by a two-step method in which both steps were carried out in one-pot. The conversion of 2 to N-(3,5-dimethyladamantane-1-yl)acetylamide (3) was synthesized first in mixture of sulfuric acid 96-98% and nitric acid 64-65% at 25 ºC for 2.5 h and then in acetonitrile at 40 ºC for 3.5 h as a key step. The yield of this process reached to 98%. Next, the deacetylation of 3 with potasium hydroxide in mixture of water-ethylene glycol at 140 ºC for 15 h to get memantine base which was then converted into memantine hydrochloride (1) by aq. HCl 14% (yield of 93%). Overall yield of this synthetic route was 91.65%. The advantages of this process is saving time, solvents, reagents and giving a higher yield as compared to reported procedures.


1,3-Dimethyladamantane, Acetonitrile, Memantine hydrochloride, N-Acetyl-1-amino-3,5-dimethyladamantane.

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