Methyl iodide → 4-[(2S,3S,4S)-2-ethyl-3-hydroxy-4-methyl-5-oxopyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile

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Reaction Steps

To a solution of diisopropylamine (0.603 mL) in tetrahydrofuran (8 mL) was added dropwise n-butyllithium-hexane solution (2.56 mL, 1.6 mol/L) at −78° C., the mixture was stirred for 1 hr, and a solution of 4-[(2S,3S)-2-ethyl-3-hydroxy-5-oxopyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile (490 mg) in tetrahydrofuran (6 mL) was added dropwise. The mixture was stirred at −78° C. for 30 min, iodomethane (0.510 mL) was added dropwise at −78° C., and the mixture was stirred at 0° C. for 1 hr. Aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=30/1→1/4) and further purified by basic silica gel chromatography (eluent: hexane/ethyl acetate=30/1→1/4) to give the title compound as a colorless solid (yield: 66.5 mg, 13%).

Provenance & Evidence