Vu Binh Duong, Ho Ba Ngoc Minh, Pham Van Hien, Phan Dinh Chau
The Drug R&D Center, Vietnam Military Medical University, No. 160, Phunghung Street, Phuc La Ward, Hadong District, Hanoi 12108, Vietnam.
School of Chemical Engineering, Hanoi University of Science and Technology, No. l, Daicoviet Street, Bach Khoa Ward, Haibatrung District, Hanoi 11600, Vietnam.
ACS Omega. 2020 Jun 25;5(26):16085-16088. doi: 10.1021/acsomega.0c01589. eCollection 2020 Jul 7.
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 -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.
盐酸美金刚是一种用于治疗阿尔茨海默病的药物。已经报道了多种制备盐酸美金刚的方法。这些方法从1,3 - 二甲基金刚烷开始，多达使用三到四个反应步骤来制备盐酸美金刚，总收率在54%至77%之间。在本文中，开发了一种从1,3 - 二甲基金刚烷经1 - 甲酰胺基 - 3,5 - 二甲基金刚烷简单、简洁的两步合成盐酸美金刚的方法，总收率提高到了83%。在第一步中，3,5 - 二甲基金刚烷与甲酰胺和硝酸反应，以98%的收率得到1 - 甲酰胺基 - 3,5 - 二甲基金刚烷，随后1 - 甲酰胺基 - 3,5 - 二甲基金刚烷用盐酸水溶液水解，以85%的收率得到盐酸美金刚。该方法可以很容易地应用于工业规模。
