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

To a solution of diisopropylamine (0.291 mL) in tetrahydrofuran (8 mL) was added dropwise n-butyllithium-hexane solution (1.24 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-methoxybenzonitrile (206.5 mg) in tetrahydrofuran (6 mL) was added dropwise. The mixture was stirred at −78° C. for 30 min, iodomethane (0.247 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) to give the title compound as a colorless solid (yield: 108.8 mg, 50%).

1. stirringThe mixture was stirred at −78° C. for 30 min
2. stirringthe mixture was stirred at 0° C. for 1 hr
3. extractionthe mixture was extracted with ethyl acetate
4. dry with materialThe extract was dried over anhydrous magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=30/1→1/4)

ORD record

ord-8b47903fec044b97a5887b991560b6c0

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08420694B2