Ammonium Chloride → 3-Cyclopentyl-1-(2,6-dimethylphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester

Temperature

-50 °C

LHMDS (1 M solution in THF, 2.4 mL, 2.4 mmol) was added slowly to a cooled (−50° C.) solution of 1-(2,6-dimethylphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (494 mg, 2 mmol) in THF (5 mL). Stirred at −50° C. for 5 min then warmed to 0° C. and stirred further for 5 min. After cooling back to −50° C., iodocyclopentane (462.5 μL, 4 mmol) was added and the resulting reaction mixture was warmed to room temperature and stirred for 2 h. Saturated aqueous NH4Cl solution (10 mL) was added, and the aqueous solution was extracted with EtOAc (3×25 mL). The combined organic layer was washed with water (50 mL), brine (50 mL), dried (Na2SO4) and evaporated. The residue was purified by flash chromatography (SiO2, 20→50% EtOAc/hexanes) to give 3-cyclopentyl-1-(2,6-dimethylphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (120 mg, 19% yield). LC-MS: Rt (retention time): 2.54 min, MS: (ES) m/z 316.4 (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 aqueous solution was extracted with EtOAc (3×25 mL)
8. washThe combined organic layer was washed with water (50 mL), brine (50 mL)
9. dry with materialdried (Na2SO4)
10. customevaporated
11. customThe residue was purified by flash chromatography (SiO2, 20→50% EtOAc/hexanes)

ORD record

ord-694f0bb7bfba447a85677d7c55e93240

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716494B2