Synthesis 2020; 52(19): 2828-2832
DOI: 10.1055/s-0040-1707399
psp
© Georg Thieme Verlag Stuttgart · New York

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

Claudia Cavarischia
a  ANGELINI PHARMA S.p.A., RR&D, Piazzale della Stazione snc, 00071 S. Palomba-Pomezia (RM), Italy   Email: [email protected]
,
Alex Comely
b  ENANTIA, Baldiri Reixac 10, 08028 Barcelona, Spain
,
Marta Écija
b  ENANTIA, Baldiri Reixac 10, 08028 Barcelona, Spain
,
Tommaso Iacoangeli
a  ANGELINI PHARMA S.p.A., RR&D, Piazzale della Stazione snc, 00071 S. Palomba-Pomezia (RM), Italy   Email: [email protected]
,
Mireia Pastó
b  ENANTIA, Baldiri Reixac 10, 08028 Barcelona, Spain
,
Lavinia Silvestri
a  ANGELINI PHARMA S.p.A., RR&D, Piazzale della Stazione snc, 00071 S. Palomba-Pomezia (RM), Italy   Email: [email protected]
,
a  ANGELINI PHARMA S.p.A., RR&D, Piazzale della Stazione snc, 00071 S. Palomba-Pomezia (RM), Italy   Email: [email protected]
› Author Affiliations
Further Information

Publication History

Received: 30 March 2020

Accepted after revision: 30 April 2020

Publication Date:
25 May 2020 (online)


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.

Supporting Information

 
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