Toluene → (R)-6-Methyl-3-azabicyclo[3.2.0]heptane-1,3-dicarboxylic acid 3-benzyl ester 1-methyl ester

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Reaction Steps

A 0.5 M solution of potassium hexamethyldisilazide in toluene (33 mL, 16.5 mmol) was added dropwise to a solution of 4-[(S)-2-iodo-1-(methyl)ethyl]pyrrolidine-1,3-dicarboxylic acid 1-benzyl ester 3-methyl ester (6.4 g, 14.8 mmol) in anhydrous tetrahydrofuran (100 mL) in an argon atmosphere at −78° C. After completion of dropwise addition, the mixture was stirred at the same temperature for 30 minutes. An ammonium chloride solution was added, and the mixture was heated to room temperature. After extraction with ethyl acetate, drying over magnesium sulfate, and filtration, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:0→7:3) to give 3.5 g (78%) of the diastereomer mixture title compound as a colorless oil. The diastereomers were used for the next step without separation.

Provenance & Evidence