Acetic Acid → 4-[(3S,4S,5S)-3-benzyl-4-hydroxy-5-methyl-2-oxopyrrolidin-1-yl]-2-chlorobenzonitrile

Temperature

-78 °C

A solution of diisopropylamine (0.150 mL) in THF (8 mL) was cooled to −78° C., and n-butyllithium-hexane solution (0.648 mL, 1.6 mol/L) was added dropwise. After the completion of the dropwise addition, the mixture was stirred at −78° C. for 1 hr. Subsequently, a solution of 2-chloro-4-[(2S,3S)-3-hydroxy-2-methyl-5-oxopyrrolidin-1-yl]benzonitrile (100 mg) in THF (2.5 mL) was added dropwise, and the mixture was further stirred at −78° C. for 30 min. A solution of benzyl bromide (0.16 mL) in THF (1.5 mL) was added dropwise at −78° C., and the mixture was further stirred at −78° C. to −30° C. for 1 hr. Acetic acid (1.0 mL) was added to the reaction mixture, and the mixture was warmed to room temperature. Water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, 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→1/2) to give the title compound as a colorless solid (yield: 40.8 mg, 30.0%).

1. additionn-butyllithium-hexane solution (0.648 mL, 1.6 mol/L) was added dropwise
2. additionAfter the completion of the dropwise addition
3. stirringthe mixture was further stirred at −78° C. for 30 min
4. stirringthe mixture was further stirred at −78° C. to −30° C. for 1 hr
5. temperaturethe mixture was warmed to room temperature
6. extractionthe mixture was extracted with ethyl acetate
7. washThe extract was washed with saturated brine
8. dry with materialdried over anhydrous magnesium sulfate
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=50/1→1/2)

ORD record

ord-5358f2216c04454b8402b452f224e5a8

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08420694B2