A Convenient, Scalable Process for the Preparation and Purification of Calcium Acamprosate

Abstract

Calcium acamprosate (Campral, N-acetylhomotaurine calcium salt) is a well-established drug for the treatment of alcohol dependence. Its preparation is generally based on a three-step process with some remarkable drawbacks. To avoid these flaws, we have developed a direct, scalable, one-pot procedure for the preparation of calcium acamprosate entailing the nucleophilic opening of readily available 1,3-propanesultone with potassium acetamide (from acetamide and potassium tert-butoxide) in N,N-dimethylformamide solution, followed by in situ cation exchange by addition of calcium chloride at controlled pH, addition of 2-propanol (IPA) as a cosolvent, and removal of potassium chloride by selective precipitation. Calcium acamprosate (purity higher than 95%) is thus obtained in the commercial crystalline form in 74–77% yield.

Key words

acetamide - calcium acamprosate - cation exchange - homotaurine­ - potassium tert-butoxide - sultone opening

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