Hydrochloric Acid → (1S,5R)-4,6-dioxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-ylcarboxylic acid tert-butyl ester

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Reaction Steps

(3S)-3-(2-Methoxycarbonyl-1-ethyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (35.0 g, 93.2 mmol) was dissolved in tetrahydrofuran (1 L). A 2 M lithium diisopropylamide/heptane/tetrahydrofuran/ethylbenzene solution (100 mL, 200 mmol) was added dropwise in a nitrogen atmosphere at an internal temperature of −69° C. over 30 minutes. After stirring at the same temperature for one hour, the reaction solution was poured into a 1N hydrochloric acid solution (2 L) in an ice bath, followed by extraction with ethyl acetate (2 L, 1 L). The organic layers were combined, washed with brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the precipitated solid was collected by filtration to give 22.2 g of the title compound as pale red crystals. The filtrate was further concentrated to give 2.88 g of the title compound as pale red crystals. The filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (hexane:ethyl acetate=1:1) to give 2.09 g of the title compound as colorless crystals.

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