Novel Synthetic Industrial Approach for Efficient Synthesis of Baclofen through C–C Bond Formation

Abstract

Baclofen is an active pharmaceutical ingredient (API) used for the treatment of muscle spasticity. We describe our efforts to develop a novel synthetic approach via C-C bond formation and the cost-effective process of Baclofen. The synthesis involved a two-step approach via C-C bond formation using the extensively and commercially available starting material 4-chlorobenzyl cyanide and chloroacetic acid as a reagent in an aprotic solvent, followed by reduction of the nitrile functional group. The synthetic route of baclofen has been demonstrated to be commercially viable, cost-effective, and environmentally friendly. Execution of the developed process led to the isolation of (+) baclofen in an overall yield of 60% at a multi-kilogram scale > 99.5 % HPLC purity. This article also discusses the cost-effectiveness of the process, impurity profiling, material quality, and polymorphic form. Key words Baclofen, polymorph, C- alkylation, Nitrile reduction.