2,2,2-Trifluoroethyl trifluoromethanesulfonate → tert-Butyl [(3S,5S)-5-(2-fluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)piperidin-3-yl]carbamate

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Reaction Conditions

Reaction Steps

To a pre-cooled 0° C. solution of tert-butyl[(3S,5S)-5-(2-fluorophenyl)-2-oxopiperidin-3-yl]carbamate (0.59 g, 1.93 mmol) in tetrahydrofuran:N-methyl-2-pyrrolidinone (2:1, 18 mL) was added lithium bis(trimethylsilyl)amide (2.29 mL, 2.29 mmol, 1 M in THF) and the mixture was stirred at 0° C. for 30 min. 2,2,2-Trifluoroethyl trifluoromethanesulfonate (0.33 mL, 2.29 mmol) was added and the resulting mixture was stirred at 0° C. for 4 h. The mixture was diluted with water and extracted with ethyl acetate (3×). The combined organic extracts were washed with water, brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (0% ethyl acetate→100% ethyl acetate/hexane) was followed by separation of the cis/trans diastereoisomers using normal-phase HPLC using a ChiralPak® AD column, eluting with 60% ethanol in hexanes to afford the title compound as the second diastereomer to elute. MS: m/z=391.2 (M+1).

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