Methyl iodide → (S)-1-(2,6-dimethylphenyl)-3-isobutyl-4-methyl-5-oxo-pyrrolidine-3-carboxylic acid methyl ester

LHMDS (1 M solution in THF, 1.78 mL, 1.78 mmol) was added slowly to a cooled (−50° C.) solution of (S)-1-(2,6-dimethylphenyl)-3-isobutyl-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (prepared from step e, 450 mg, 1.48 mmol) in THF (10 mL). After 5 min, iodomethane (185 μL, 2.97 mmol) was added at −50° C. and the resulting reaction mixture was immediately warmed to room temperature and stirred further for 2 h. Saturated aqueous NH4Cl solution (25 mL) was added, and the solution was extracted with EtOAc (3×50 mL). The combined organic layers were washed with water (50 mL), brine (50 mL), dried (Na2SO4) and evaporated. The residue was purified by flash chromatography (SiO2, 20→60% MTBE/hexanes) to give (S)-1-(2,6-dimethylphenyl)-3-isobutyl-4-methyl-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (130 mg, 28% yield). LC-MS: Rt (retention time): 2.68 min, MS: (ES) m/z 318.2 (M+H+).

1. customthe resulting reaction mixture
2. extractionthe solution was extracted with EtOAc (3×50 mL)
3. washThe combined organic layers were washed with water (50 mL), brine (50 mL)
4. dry with materialdried (Na2SO4)
5. customevaporated
6. customThe residue was purified by flash chromatography (SiO2, 20→60% MTBE/hexanes)

ORD record

ord-1f70ad8fc7764d73ae4945ff93b96a41

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08293925B2