Open AccessTwo Step Cost-Saving Process for Industrial Scale Production of 1-Amino-3,5-dimethyladamantane Hydrochloride (An Anti-Alzheimer’s Drug)
Author(s) -
Thi Hong Tham Nguyen,
Viet Duc Le,
Ngo Sy Thinh,
Thi Hong Thanh Nguyen,
Dinh Chau Phan,
Binh Duong Vu
Publication year - 2022
Publication title -
asian journal of chemistry/asian journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.145
H-Index - 34
eISSN - 0975-427X
pISSN - 0970-7077
DOI - 10.14233/ajchem.2022.23447
Subject(s) - chemistry , yield (engineering) , hydrochloride , reagent , sulfuric acid , nitric acid , acetonitrile , nuclear chemistry , organic chemistry , metallurgy , materials science
This work presents a predominant cost-saving process for the industrial scale synthesis of memantinehydrochloride (1) from 1,3-dimethyladamantane (2) by a two-step method in which both steps werecarried out in one-pot. The conversion of 2 to N-(3,5-dimethyladamantane-1-yl)acetylamide (3) wassynthesized first in mixture of sulfuric acid 96-98% and nitric acid 64-65% at 25 ºC for 2.5 h and then inacetonitrile at 40 ºC for 3.5 h as a key step. The yield of this process reached to 98%. Next, thedeacetylation of 3 with potasium hydroxide in mixture of water-ethylene glycol at 140 ºC for 15 h toget 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 issaving time, solvents, reagents and giving a higher yield as compared to reported procedures.