Efficient Synthesis of (S)-3-(4-Fluorophenyl)morpholin-2-one, a Key Chiral Intermediate of Aprepitant

A facile, economical, and practical method for the preparation of (S)-3-(4-fluorophenyl)morpholin-2-one [(S)-9] has been developed from ethyl 2-(4-fluorophenyl)-2-oxoacetate (7) in three steps through cyclization, hydrogenation, and resolution, providing a new and convenient access to the key intermediate of antiemetic drug aprepitant.