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Objectives: To develop a short and simple method for preparation of amantadine hydrochloride from adamantane. Methods: The method involved two steps: conversion of adamantane in the presence of nitric acid and acetonitrile to N-(1-adamantyl)-acetamide followed by deacylation with sodium hydroxide in a mixture of water and propylene glycol and then acidification with hydrochloride acid solution to give amantadine hydrochloride. | Journal of military pharmaco-medicine no7-2017 SIMPLE PREPARATION OF AMANTADINE HYDROCHLORIDE FROM ADAMANTANE Nguyen Van Thinh*; Pham Van Hien* Dang Tuan Anh**; Vu Binh Duong*; Phan Dinh Chau** SUMMARY Objectives: To develop a short and simple method for preparation of amantadine hydrochloride from adamantane. Methods: The method involved two steps: conversion of adamantane in the presence of nitric acid and acetonitrile to N-(1-adamantyl)-acetamide followed by deacylation with sodium hydroxide in a mixture of water and propylene glycol and then acidification with hydrochloride acid solution to give amantadine hydrochloride. Results: The structure of the obtained amantadine hydrochloride with an overall yield of 71.56% and intermediates were confirmed by IR, MS, 1H-NMR, 13C-NMR. Conclusion: The described procedure offers a very simple workup compared to that reported previously, therefore it represents an efficient alternative method for the synthesis of amantadine hydrochloride. * Keywords: Adamantane; Nitric acid; Acetonitrile, N-(1-adamantyl) acetamide; Amantadine hydrochloride. INTRODUCTION Amantadine hydrochloride (1aminoadamantane hydrochloride, 1) is an antiviral drug used to treat certain influenza infections (type A) and is the first antiviral agent licensed for use in the United States. The medicine has worked against most types of influenza virus and was used to treat type A virus in Asia influenza epidemic in 1966. Recently, it has also been used as an antidyskinetic agent for the treatment of Parkinson’s disease. In the current US Pharmacopoeia, USP38-NF33, there are three monographs of amantadine including amantadine hydrochloride (p.2160), capsule of amantadine hydrochloride (p.2161), and oral solution of amantadine (p.2162). Many developing countries, such as Vietnam and China, are using amantadine for its antiviral and anti-Parkinson effects. Since then, many papers have been reported regarding synthesis of amantadine (5) and 1 [[1, 2, 3, 4, 5,