Hydrogen Peroxide → (3S)-3-(3-hydroxy-1-propyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester

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Reaction Conditions

Reaction Steps

(3S)-3-Allyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (more polar isomer) (51.5 g, 0.156 mol) was dissolved in tetrahydrofuran (780 mL). Then, a 0.5 M solution of 9-BBN in tetrahydrofuran (345 mL, 0.173 mol) was added dropwise from a dropping funnel in a nitrogen stream under cooling and stirring in an ice salt bath at an internal temperature of 0° C. After completion of the dropwise addition, the mixture was stirred at the same temperature for 30 minutes and subsequently at room temperature for 1.5 hours. The mixture was cooled again in an ice salt bath, and a 0.5 M solution of 9-BBN in tetrahydrofuran (156 mL, 78 mmol) was added dropwise from a dropping funnel at an internal temperature of 2° C. After completion of the dropwise addition, the mixture was stirred at the same temperature for 30 minutes and then at room temperature for 1.5 hours. The mixture was cooled again in an ice salt bath, and a 0.5 M solution of 9-BBN in tetrahydrofuran (120 mL, 60 mmol) was added dropwise from a dropping funnel at an internal temperature of 2° C. After completion of the dropwise addition, the mixture was stirred at the same temperature for 30 minutes and then at room temperature for one hour. The mixture was cooled again in an ice salt bath, and 780 mL of a 1N sodium hydroxide solution was added dropwise at an internal temperature of 0° C. over 15 minutes (internal temperature: 2° C. or less). The mixture was stirred for 10 minutes, and then 78 mL of a 30% hydrogen peroxide solution was added dropwise at an internal temperature of 4° C. or less over 30 minutes. After vigorously stirring at the same temperature for 30 minutes, 1.6 L of diethyl ether was added. After addition of 1.6 L of a saturated sodium bicarbonate solution, the layers are separated, and the aqueous layer was extracted with diethyl ether. The combined organic layers were washed with brine, a 10% citric acid solution, a 10% sodium thiosulfate solution, and then brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated, and the resulting residue was subjected to flash silica gel column chromatography and eluted with a mixed solvent of methanol-chloroform (1:50, v/v). The fractions containing the target substance were combined and concentrated and dried under reduced pressure to give 40.61 g (74.9%) of the title compound as a colorless oil. Further, part of the title compound was purified by recrystallization from diethyl ether to provide needle-like crystals which were used for X-ray crystallography. As a result, the absolute configuration at the 3-position of this product was determined as a (3S)-configuration.

Provenance & Evidence