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

Abstract

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.

GRAPHICAL ABSTRACT

Keywords:

• Aprepitant
• chiral intermediate
• DBTA
• resolution

SUPPLEMENTAL MATERIAL

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