Tetrahydrofuran → 1-(2,6-Dimethyl-phenyl)-3-ethyl-4-hydroxy-5-oxo-pyrrolidine-3-carboxylic acid methyl ester

Temperature

-50 °C

LHMDS (1 M solution in THF, 6 mL, 6 mmol) was added slowly to a cooled (−50° C.) solution of 1-(2,6-dimethylphenyl)-3-ethyl-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (prepared from step a, 1.1 g, 4 mmol) in THF (15 mL). The solution was stirred at −50° C. for 5 min then warmed to 0° C. and stirred for an additional 5 min. After cooling back to −50° C., (R,S)-camphorsulfonyloxaziridine (1.1 g, 4.8 mmol) was added and the resulting reaction mixture was warmed to room temperature and stirred for 2 h. Saturated aqueous NH4Cl solution (30 mL) was added, and the solution was extracted with EtOAc (3×75 mL). The combined organic layers were washed with water (50 mL), brine (50 mL), dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (SiO2, 30→70% EtOAc/hexanes) to give 1-(2,6-dimethyl-phenyl)-3-ethyl-4-hydroxy-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (1.1 g, quantitative yield). LC-MS: Rt (retention time): 1.89 min, MS: (ES) m/z 292.1 (M+H+).

1. temperaturethen warmed to 0° C.
2. stirringstirred for an additional 5 min
3. temperatureAfter cooling back to −50° C.
4. customthe resulting reaction mixture
5. temperaturewas warmed to room temperature
6. stirringstirred for 2 h
7. extractionthe solution was extracted with EtOAc (3×75 mL)
8. washThe combined organic layers were washed with water (50 mL), brine (50 mL)
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by flash chromatography (SiO2, 30→70% EtOAc/hexanes)

ORD record

ord-7f5367d3aa964236a4891b2a0a38669a

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716494B2