A facile synthesis of 2-(4-((4-chlorophenyl)(hydroxy)methyl) phenoxy)-2-methylpropanoic acid: Metabolite of anti-hyperlipidemic drug Fenofibrate.

Synthesis and characterization of drug metabolites has emerged as an important area of research in consideration to the significant contribution of studies on metabolites in drug research. The present work comprises synthesis of 2-(4-((4-chlorophenyl)(hydroxy)methyl) phenoxy)-2-methylpropanoic acid, a metabolite of anti-hyperlipidemic drug fenofibrate. The desired compound was prepared by two different synthetic routes.

A facile and chemoselectivity in synthesis of 4-chloro-N-(4-((1-hydroxy-2-methylpropan-2-yl)oxy)phenethyl)benzamide, the alcohol derivative of Bezafibrate.

A facile method for the reduction of carboxylic acid group of Bezafibrate, an approved drug, is described. The selective reduction of carboxylic acid group to corresponding alcohol was carried out by activation of the carboxylic acid moiety via mixed anhydride followed by the addition of stoichiometric amount of NaBH and methanol to obtain the first alcohol variant of Bezafibrate. The reaction was completed in 5-10 min in excellent yield and purity.

Chemoselective Reduction of Fenofibric Acid to Alcohol in the Presence of Ketone by Mixed Anhydride and Sodium Borohydride.

A highly efficient and facile protocol for the selective reduction of carboxylic acid of Fenofibric acid to corresponding alcohol was developed. The selective reduction was carried out by activation of carboxylic acid by mixed anhydride followed by the reaction of sodium borohydride in presence of methanol. This is the first example of chemoselective reduction of carboxylic acid to alcohol in presence of a ketone without any external catalyst or ligand in a single step.