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

Temperature

-78 °C

A solution of diisopropylamine (0.150 mL) in THF (7 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 (1.5 mL) was added dropwise, and the mixture was further stirred at −78° C. for 30 min. Acetone (0.124 mL) was added dropwise at −78° C., and the mixture was further stirred at −20° C. to −78° C. for 40 min. 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=10/1→1/3) to give the title compound as a colorless solid (yield: 30.1 mg, 24.5%).

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 −20° C. to −78° C. for 40 min
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=10/1→1/3)

ORD record

ord-99a4134bfc234a48810b21e455ddbe19

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08420694B2