1-Actamido-3,5-dimethyladmantane (19982-07-1) 's Synthetic route

Amidation of 1-bromo-3,5-dimethyladamantane catalyzed with manganese compounds and complexes

Khusnutdinov  Shchadneva  Khisamova

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

Le, Viet Duc  Ngo, Sy Thinh  Nguyen, Thi Hong Tham  Nguyen, Thi Hong Thanh  Phan, Dinh Chau  Vu, Binh Duong

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-(3,5dimethyladamantane-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.