Lithium Hexamethyldisilazide → (1S,5R)-5-Fluoro-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.2.0]heptane-1-carboxylic acid tert-butyl ester

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Reaction Steps

A 1.0 M solution of lithium hexamethyldisilazide in tetrahydrofuran (5.02 mL) was added dropwise to a solution of (3S)-3-(2-bromoethyl)-4-fluoro-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (2.04 g, 4.92 mmol) in tetrahydrofuran (40 mL) in a nitrogen atmosphere at −72° C. over 10 minutes. The mixture was stirred at the same temperature for 15 minutes and then at 0° C. for 30 minutes. The reaction was quenched with a 10% citric acid solution (2 mL) and then poured into a mixture of ethyl acetate (100 mL) and a 10% citric acid solution (20 mL). After extraction with ethyl acetate (150 mL), the organic layer was washed with brine (20 mL×2), dried over anhydrous sodium sulfate, and filtered. The filtrate was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to give 1.41 g (86%) of the title compound as a white solid.

Provenance & Evidence