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

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

doi:10.14233/ajchem.2022.23447

Issue

Vol. 34 No. 2 (2022): Vol 34 Issue 2

Issue Published : January 11, 2022

This work is licensed under a Creative Commons Attribution 4.0 International License.

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

https://doi.org/10.14233/ajchem.2022.23447

Thi Hong Tham Nguyen

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

Viet Duc Le

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

Sy Thinh Ngo

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

Thi Hong Thanh Nguyen

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

Dinh Chau Phan

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

Binh Duong Vu

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

Corresponding Author(s) : Binh Duong Vu

vbduong2978@gmail.com

Asian Journal of Chemistry, Vol. 34 No. 2 (2022): Vol 34 Issue 2
Article Published : January 11, 2022

Abstract

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.

Keywords

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

Hong Tham Nguyen, T., Duc Le, V., Thinh Ngo, S., Hong Thanh Nguyen, T., Chau Phan, D., & Duong Vu, B. (2022). Two Step Cost-Saving Process for Industrial Scale Production of 1-Amino-3,5-dimethyladamantane Hydrochloride (An Anti-Alzheimer’s Drug). Asian Journal of Chemistry, 34(2), 251–255. https://doi.org/10.14233/ajchem.2022.23447

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References

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References

J. Liu, L. Chang, Y. Song, H. Li and Y. Wu, Front. Neurosci., 13, 43 (2019); https://doi.org/10.3389/fnins.2019.00043

R. Crupi, D. Impellizzeri and S. Cuzzocrea, Front. Mol. Neurosci., 12, 20 (2019); https://doi.org/10.3389/fnmol.2019.00020

M.K. Madhra, M. Sharma and C.H. Khanduri, Org. Process Res. Dev., 11, 922 (2007); https://doi.org/10.1021/op700138p

M. McLaughlin, S.G. Rubio, U. Tilstam, O.A.C. Antunes, T. Laird, G.D. Yadav and A. Zlota, Org. Process Res. Dev., 11, 2 (2007); https://doi.org/10.1021/op600268a

O.P. Tyagi, G.S. Ramanjaneyulu, B. Mohan, I.V.S. Kumar and K.N.A. Rao, WO Patent 132476A2 (2007).

R.U. Roy, P. Chan, R. Kumar and D.S. Dhar, WO Patent 062472 A2 (2008).

E. Vigano, M. Arrighi, R. Molteni, S. Lanfranconi and E. Landonio, New Process for the Synthesis of Moguisteine, EP2231627A2 (2006).

M.R. Gold, H. Koller and M. Pyerin, Process for Manufacturing Adamantane Derivatives with High Yield, US Patent 8796491B2 (2014).

E.A. Ivleva and Y.N. Klimochkin, Org. Prep. Proced. Int., 49, 155 (2017); https://doi.org/10.1080/00304948.2017.1291004

R. Ponnaiah, A. Prasad, P.M. Rana, K.S. Kanzariya and M.B. Dolia, WO Patent 067252 A1 (2010).

K.A. Ovchnikov, E.A. Ivleva and J.N. Klimmochkin, RU Patent 2541545 C2 (2015).

P.R. Schreiner and L. Wanka, WO Patent 010362 A1 (2006).

P.K. Jauhari, WO Patent 153806A2 (2009).

F.A.M., Huber, G. Gallo and D.F. Carla, WO Patent 115334 A2 (2009).

M.S. Reddy, S. Eswaraiah, G.V. Reddy and C. Suresh, WO Patent 057140 A2 (2009).

G. Quack and M.R. Gold, Process for Preparing Memantine, US Patent 0282100A1 (2011).

S.L. Pathi and R.N. Kankan, WO Patent 007351A1 (2010).

P.R. Schreiner, A.A. Fokin, L. Wanka and D.M. Wolfe, Method for Producing 1-Formamido-3,5 dimethyladamantane, US Patent 8138375B2 (2012).

S. Wang, J. Li, J. Du, L. Wang and L. Huang, Method of Synthesizing Amantadine Hydrochloride, CN Patent 1556094A (2004).

B.D. Vu, B.N.M. Ho, V.H. Tran, V.H. Pham and D.C. Phan, Org. Prep. Proced. Int., 52, 463 (2020); https://doi.org/10.1080/00304948.2020.1785807

B.D. Vu, B.N.M. Ho, V.H. Pham and D.C. Phan, ACS Omega, 5, 16085 (2020); https://doi.org/10.1021/acsomega.0c01589

F. Zhang, M. Hu, L. Zhao and M. Ge, Method of Preparing Memantine Hydrochloride, US Patent 7355080B2 (2008).