A SIMPLE METHOD FOR SYNTHESIS OF AMANTADINE HYDROCHLORIDEAbstract
Amantadine hydrochloride (1) is an antiviral drug currently used to treat certain influenza infections (type A). It is also used as an anti-dyskinetic agent to treat Parkinson’s disease. Several methods for the preparation of amantadine hydrochloride (1) were reported, these procedures started from adamantane (2), using procedure four reaction steps to obtain amantadine hydrochloride with an overall yield of 46-58%. In this article, we present a convenient two-step procedure for the synthesis of 1 from 1-bromoadamantane (3) and acetylamide in the presence of sulfuric acid via N-(1-adamantyl) acetamide (4) in one-pot with an overall yield of 74%. The procedure was also optimized to reduce the use of toxic reagents and solvents to make it to safer and more environmentally friendly. The procedure can be considered as more suitable for large-scale production of amantadine hydrochloride. The structure of the obtained amantadine hydrochloride was confirmed by MS, IR, 1H-NMR and 13C-NMR.
Binh Duong Vu, Thi Phuong Dung Phan *, Thi Van Tran, Anh Tuan Dang, Phuong Linh Nguyen and 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.
18 February 2021
05 June 2021
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01 February 2022