Efficient synthesis of (R)-3-amino-1,1,1-trifluoropropan-2-ol via a Dakin–West reaction followed by enantioselective reduction

An efficient, chromatography-free asymmetric synthesis of (R)-3-amino-1,1,1-trifluoropropan-2-ol was developed for large scale production of a cholesterol ester transfer protein (CETP) inhibitor. The synthesis features a new efficient route to a β-amino trifluoromethylketone involving a modified Dakin–West reaction followed by an asymmetric hydrogenation or an enzymatic reduction of the resulting ketone to the alcohol.

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(R)-N-(3,3,3-Trifluoro-2-hydroxypropyl)benzamideC10H10F3NO2[α]D20=-28.4 (c, 1.0, MeOH)Source of chirality: chiral hydrogenationAbsolute configuration: (R)