Synthesis of methyl (R)-3-(4-fluorophenyl)glutarate via enzymatic desymmetrization of a prochiral diester

► A procedure of enzymatic desymmetrization of a prochiral diester was developed. ► An aqueous-organic phase containing phosphate buffer and MTBE was used. ► 95.6% ee of (R)-3-MFG was obtained, together with the highest yield of 92.6%. ► Novozym 435 showed an excellent operational stability.