Effective synthesis of (S)-3,5-bistrifluoromethylphenyl ethanol by asymmetric enzymatic reduction

The synthesis of (S)-3,5-bistrifluoroniethylphenyl ethanol, a pharmaceutically important alcohol intermediate for the synthesis of NK-1 receptor antagonists, was demonstrated from a ketone via asymmetric enzymatic reduction. The isolated enzyme alcohol dehydrogenase from Rhodococcus erythropolis reduced the poorly water soluble substrate with excellent ee (> 99.9%) and good conversion (> 98%). The optimized process was demonstrated up to pilot scale using high substrate concentration (390 mM) using a straightforward isolation process achieving excellent isolation yields (> 90%) and effective space time yield (100-110 g/L d). Process improvements, demonstrated at preparative scale, increased the substrate concentration to 580 mM achieving a space time yield of 260 g/L d. (c) 2006 Elsevier Ltd. All rights reserved.