A CONCISE TWO-STEP METHOD FOR PREPARATION OF MEMANTINE HYDROCHLORIDE FROM 1, 3-DIMETHYLADAMANTANEAbstract
Memantine hydrochloride is a medicine used to medicate patients with moderately severe to severe Alzheimer’s disease and other neurodegenerative disorders; because of mechanisms of neuroprotection, the efficiency of memantine have been delivered in preclinical and clinical experiments. Several approaches for preparing memantine hydrochloride have been announced. The process began with 1,3-dimethyladamantane or 1-bromo-3,5-dimethyladamantane using three or four reaction steps for the production of memantine hydrochloride, with overall yield fluctuating from 39% to 63%. In this article, a concise two-step for the synthesis of memantine hydrochloride from 1,3-dimethyladamantane via 1-acetamido-3,5-dimethyl-adamantane with an overall yield of 85% was developed. The parameters of the procedure were also optimized with a view to lessening the utilization of toxic solvents and reagents, making it more eco-friendly. And in particular, the condition reaction are specified in the preparation of 1-acetamido-3,5-dimethyladamantaneasreaction temperature = 70 ºC, time reaction =2.5 hrs, molar ratio of (acid nitric: acetonitril: 1,3-dimethyladamantane) = 7:10:1; in the synthesis of memantine hydrochloride as reaction temperature = 130 ºC, time reaction = 8 h, molar ratio of (NaOH: HCl:1-acetamido-3,5-dimethyl-adamantane) = 4:6:1; weight ratio of (PG: 1-acetamido-3,5-dimethyl-adamantane) = 2.5:1. The procedure can be regarded as being suitable for producing of Memantine hydrochloride on a large scale.
Thi Hong Tham Nguyen, Trong Diep Nguyen, Dinh Chau Phan and Binh Duong Vu *
Vietnam Military Medical University, No.160, Phung Hung str., Phuc La ward, Ha Dong district, Hanoi, Vietnam.
27 January 2021
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