Iodoethane → 1-(2,6-Dimethylphenyl)-3-ethyl-5-oxo-pyrrolidine-3-carboxylic acid methyl ester

Temperature

-50 °C

LHMDS (1 M solution in THF, 24.3 mL, 24.3 mmol) was added slowly to a cooled (−50° C.) solution of 1-(2,6-dimethylphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (5 g, 20.24 mmol) in THF (25 mL). The solution was stirred at −50° C. for 5 min then warmed to 0° C. and stirred further for 5 min. After cooling back to −50° C., iodoethane (3.27 mL, 40.48 mmol) was added and the resulting reaction mixture was warmed to room temperature and stirred for 2 h. Saturated aqueous NH4Cl solution (50 mL) was added, and the solution was extracted with EtOAc (3×100 mL). The combined organic layer were washed with water (100 mL), brine (100 mL), dried (Na2SO4) and evaporated. The residue was purified by flash chromatography (SiO2, 20→50% EtOAc/hexanes) to give 1-(2,6-dimethylphenyl)-3-ethyl-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (3.3 g, 59% yield). LC-MS: Rt (retention time): 2.21 min, MS: (ES) m/z 276.1 (M+H+).

1. temperaturethen warmed to 0° C.
2. stirringstirred further for 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 (3×100 mL)
8. washThe combined organic layer were washed with water (100 mL), brine (100 mL)
9. dry with materialdried (Na2SO4)
10. customevaporated
11. customThe residue was purified by flash chromatography (SiO2, 20→50% EtOAc/hexanes)

ORD record

ord-40e9c85400c64c8095d6f8d920ae2b6e

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716494B2