反应详情

NaH (60% dispersed in mineral oil, 50 mg, ˜2.0 mmol) was added slowly to a cooled (0° C.) solution of 1-(2,6-dimethylphenyl)-3-ethyl-4-hydroxy-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (prepared from step b, 146 mg, 0.5 mmol) in THF (5 mL). After stirring for 5 min, MeI (62.5 μL, 1 mmol) was added and the resulting reaction mixture was slowly warmed to room temperature and stirred further for 12 h. Saturated aqueous NH4Cl solution (10 mL) was added, and the solution was extracted with EtOAc (3×25 mL). The combined organic layer were washed with water (50 mL), brine (50 mL), dried (Na2SO4) and evaporated. The residue was purified by flash chromatography (SiO2, 10→50% EtOAc/hexanes) to give 1-(2,6-dimethylphenyl)-3-ethyl-4-methoxy-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (70 mg, 46% yield). LC-MS: Rt (retention time): 2.31, 2.44 min (two diastereomers), MS: (ES) m/z 306.2 (M+H+).

1. customthe resulting reaction mixture
2. stirringstirred further for 12 h
3. extractionthe solution was extracted with EtOAc (3×25 mL)
4. washThe combined organic layer were washed with water (50 mL), brine (50 mL)
5. dry with materialdried (Na2SO4)
6. customevaporated
7. customThe residue was purified by flash chromatography (SiO2, 10→50% EtOAc/hexanes)