Acetic Acid → 2-chloro-4-[(2S,3S,4S)-2-ethyl-3-hydroxy-4-methyl-5-oxopyrrolidin-1-yl]benzonitrile

To a solution of diisopropylamine (0.111 mL) in tetrahydrofuran (5 mL) was added dropwise n-butyllithium-hexane solution (0.472 mL, 1.6 mol/L) at −78° C., the mixture was stirred for 1 hr, and a solution of 2-chloro-4-[(2S,3S)-2-ethyl-3-hydroxy-5-oxopyrrolidin-1-yl]benzonitrile (80 mg) in tetrahydrofuran (3 mL) was added dropwise. The mixture was stirred at −78° C. for 30 min, iodomethane (0.100 mL) was added dropwise at −78° C., and the mixture was stirred at 0° C. for 2 hr. Acetic acid (0.500 mL) was added dropwise to the reaction mixture, water was added, 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=50/1→1/3) to give the title compound as a colorless solid (yield: 10.8 mg, 13%).

1. stirringThe mixture was stirred at −78° C. for 30 min
2. stirringthe mixture was stirred at 0° C. for 2 hr
3. additionwas added
4. extractionthe mixture was extracted with ethyl acetate
5. dry with materialThe extract was dried over anhydrous magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=50/1→1/3)

ORD record

ord-9897184499ae42839424112d3078bc08

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08420694B2