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 dry tetrahydrofuran (100 ml). After cooling the solution to −78° C., a 1.68 M solution of n-butyllithium in n-hexane (28.1 ml, 47.21 mmol) was added dropwise thereinto over a period of 15 minutes. Then the liquid reaction mixture was stirred at 0° C. for 10 minutes and cooled to −78° C. Next, a solution of 4-(S)-(1-ethoxycarbonylcyclopropyl)-3-(R)-fluoro-1-[1-(S)-phenylethyl]-2-pyrrolidone (13.72 g, 42.96 mmol) in dry tetrahydrofuran (40 ml) was added dropwise thereinto over a period of 20 minutes. The liquid reaction mixture was stirred at −78° C. for 20 minutes. Then, a solution of 2,6-di-tert-butylphenol (10.63 g, 51.52 mmol) in dry tetrahydrofuran (40 ml) was added dropwise thereinto over a period of 20 minutes. The liquid reaction mixture was stirred at −78° C., for 10 minutes and then heated to room temperature. Under ice cooling, a saturated aqueous solution of ammonium chloride (200 ml) was added to the liquid reaction mixture. The organic layer was separated and the aqueous layer was extracted with diethyl ether (200 ml×2). The combined organic layer was washed with water (400 ml×2) and dried over anhydrous magnesium sulfate. After filtering, the filtrate was concentrated-under reduced pressure and the residue was subjected to flash silica gel column chromatography (eluent: n-hexane:ethyl acetate=3:1) to obtain 10.19 g (74.2%) of the title compound as a colorless oily substance.

Provenance & Evidence