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

A solution of diisopropylamine (0.208 mL) in tetrahydrofuran (8 mL) was cooled to −78° C., n-butyllithium-hexane solution (0.885 mL, 1.6 mol/L) was added dropwise, and the mixture was stirred for 1 hr. A solution of 2-chloro-4-[(2S,3R)-2-ethyl-3-hydroxy-5-oxopyrrolidin-1-yl]benzonitrile (145.5 mg) in tetrahydrofuran (2 mL) was added dropwise and the mixture was stirred at −78° C. for 1 hr. A solution of iodomethane (0.176 mL) in tetrahydrofuran (2 mL) was added dropwise at −78° C., and the mixture was stirred at −78° C. for 30 min and at 0° C. for 30 min. Water 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=50/1→1/3) to give the title compound as a colorless solid (yield: 57.0 mg, 37%).

1. additionn-butyllithium-hexane solution (0.885 mL, 1.6 mol/L) was added dropwise
2. stirringthe mixture was stirred at −78° C. for 1 hr
3. stirringthe mixture was stirred at −78° C. for 30 min and at 0° C. for 30 min
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-078f043d7fb44d7bb2f160cda06a330d

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08420694B2