Citric Acid → (1S,5S)-5-Methyl-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.2.0]heptane-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A 1.0 M solution of lithium hexamethyldisilazide in tetrahydrofuran (3.8 mL, 3.80 mmol) was added dropwise to a solution of (3S)-3-(2-bromoethyl)-4-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (1.30 g, 3.17 mmol) in tetrahydrofuran (20 mL) in a nitrogen atmosphere at −72° C. over seven minutes. The mixture was stirred at the same temperature for 30 minutes. After heating to −10° C. and stirring for 1.5 hours, a 1.0 M solution of lithium hexamethyldisilazide in tetrahydrofuran (4.0 mL, 4.0 mmol) was added over two minutes, and the mixture was stirred at 0° C. for 20 hours. A 10% citric acid solution (20 mL) was added at the same temperature. The reaction solution was poured into a mixture of ethyl acetate (100 mL) and a 10% citric acid solution (10 mL). After extraction with ethyl acetate (150 mL), the organic layer was washed with brine (30 mL), 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→1:1) to give 0.845 g (81%) of the title compound as a white solid.

Provenance & Evidence