Efficient Synthesis of (1R)‐[3,5‐Bis(trifluoromethyl)phenyl] Ethanol, a Key Intermediate for Aprepitant, an NK‐1 Receptor Antagonist

DRL‐IPD Communication Number: IPM 00029.

Abstract

Enzyme‐catalyzed efficient synthesis of (1R)‐[3,5‐bis (trifluoromethyl) phenyl] ethanol (R)‐(3), a key intermediate for aprepitant, via enantioselective transesterification of racemic 1‐[3,5‐bis (trifluoromethyl) phenyl] ethanol (RS)‐3 using vinyl acetate as the acyl donor in the presence of Candida antarctica lipase‐B (CAL‐B) in an overall yield of 84% with >99% ee is described.

Keywords:

• aprepitant
• Candida antarctica lipase‐B (CAL‐B)
• economic synthesis
• enantioselctive transesterification

Acknowledgments

The authors thank the management of Dr. Reddy's Laboratories Ltd. for supporting this work. Cooperation from the project collegues is highly appreciated.

Notes

DRL‐IPD Communication Number: IPM 00029.