Diisopropylamine → 4-(S)-(1-Ethoxycarbonylcyclopropyl)-3-(S)-fluoro-1-[1-(S)-phenylethyl]-2-pyrrolidone

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, diisopropylamine (7.22 ml, 51.52 mmol) was dissolved in anhydrous tetrahydrofuran (100 ml) to which, after cooling to −78° C., was subsequently added dropwise an n-hexane solution of 1.68 M n-butyl lithium (28.1 ml, 47.21 mmol) over a period of 15 minutes. After 10 minutes of stirring at 0° C. and subsequent cooling to −78° C., to the resulting reaction solution was added dropwise an anhydrous tetrahydrofuran solution (40 ml) of 4-(S)-(1-ethoxycarbonylcyclopropyl)-3-(R)-fluoro-1-[1-(S)-phenylethyl)-2-pyrrolidone (13.72 g, 42.96 mmol) over a period of 20 minutes. After an additional 20 minutes of stirring at −78° C., to the reaction solution was added dropwise 2,6-di-tert-butylphenol (10.63 g, 51.52 mmol) dissolved in anhydrous tetrahydrofuran (40 ml) over a period of 20 minutes. The reaction solution was stirred at −78° C. for 10 minutes and then warmed to room temperature. While cooling in an ice bath, the resulting reaction solution was mixed with a saturated ammonium chloride aqueous solution (200 ml), the organic layer was separated and then the aqueous layer was extracted with diethyl ether (200 ml×2). The organic layers were combined, washed with water (400 ml×2) and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the resulting residue was subjected to flash silica gel chromatography and eluted with an eluant of n-hexane:ethyl acetate=3:1, to thereby obtain 10.19 g (74.2%) of the title compound as a colorless oil.

Provenance & Evidence