(R)-1-(3,5-Bis(trifluoromethyl)phenyl)ethanol

Li H, et al. Organic Process Research & Development, 2015, 19(7), 695-700.

The synthesis of (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethanol, an essential chiral intermediate in EMEND production, was achieved using an immobilized ketoreductase system. The enzyme was covalently attached to EC-HFA resin, ensuring high catalytic stability in organic solvent mixtures. Experimental application involved substrate loading at 50 g/L in a biphasic system of 50% hexanes, 40% isopropanol, and 10% water, maintained at 40 °C. Under these optimized conditions, the immobilized ketoreductase efficiently reduced the prochiral ketone to the (R)-alcohol with >98% conversion and >99% enantiomeric excess (ee). The immobilized biocatalyst demonstrated excellent reusability, operating effectively in both batch and continuous-flow reactors.