Development of a scalable process for a key intermediate of (R)-metalaxyl by enzymatic kinetic resolution

摘要

A scale-up study was carried out for the enzyme-catalyzed kinetic resolution of 2-methoxyethyl N-(2,6)-dimethylphenyl)alaninate rac-3 for the preparation of ( R)-metalaxyl at 20-L scale. Immobilization of lipase PS on a polymeric support enabled the reuse of the enzyme. The unreacted enantiomer was racemized by means of acid/aldehyde catalyzed Schiff base intermediate formation. The combination of lipase PS-catalyzed hydrolytic kinetic resolution and racemization of the remaining ester gave a satisfactory reaction yield (> 80%) and high enantiomeric excess (96% ee) for one recycle.