反应详情

Tert-Butyl {(3S)-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidin-3-yl}carbamate (I-343) (4.08 g, 12.8 mmol) and methyl iodide (1.20 ml, 19.2 mmol) were dissolved in N,N-dimethylformamide (120 ml), and with cooling with ice, sodium hydride (55% w/w) (671 mg, 15.4 mmol) was added, followed by stirring for 1 hour with cooling with ice. With cooling with ice, aqueous 10% citric acid solution was added to the reaction liquid, followed by concentration under reduced pressure. The resulting residue was dissolved in ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate, then the insoluble was separated by filtration, and the residue obtained by concentration was purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=2:1→1:4, v/v) to obtain tert-butyl methyl-{(3S)-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidin-3-yl}carbamate (4.09 g, 96%) as a colorless oily substance.

1. additionwas added
2. temperaturewith cooling with ice
3. additionwas added to the reaction liquid
4. concentrationfollowed by concentration under reduced pressure
5. dissolutionThe resulting residue was dissolved in ethyl acetate
6. washwashed with saturated brine
7. dry with materialdried over anhydrous sodium sulfate
8. customthe insoluble was separated by filtration
9. customthe residue obtained by concentration
10. customwas purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=2:1→1:4, v/v)