Development of a Continuous Enzymatic Process for the Preparation of (R)-3-(4-Fluorophenyl)-2-hydroxy Propionic Acid

While many methods have been reported for the synthesis of chiral 2-hydroxy acids, few of them have proven to be reliable toward the synthesis of the title compound in terms of overall yield and enantioselectivity. Herein we describe a continuous enzymatic process for an efficient synthesis of ( R )-3-(4-fluorophenyl)-2-hydroxy propionic acid at multikilogram scale with a high space−time yield (560 g/(L·d)) using a membrane reactor. The product was generated in excellent enantiomeric excess (ee > 99.9%) and good overall yield (68−72%).