反应详情

To a stirred solution of 4-nitro-1,3-dihydro-2H-indol-2-one (5.25 g, 29.5 mmol, described in Intermediate 16) in DMF (200 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil; 1.24 g, 30.9 mmol) and the resulting mixture was stirred for 30 min. Ethyl bromoacetate (3.60 mL, 32.4 mmol) was added dropwise and the mixture was stirred at 0° C. for 1 h. A further equivalent of sodium hydride (60% dispersion in mineral oil; 1.24 g, 30.9 mmol) was added, stirring was continued for 1 h, then ethyl bromoacetate (3.00 mL, 27.1 mmol) was added dropwise. The reaction mixture was stirred for 1 h, then quenched with saturated aqueous NH4Cl (125 mL) and H2O (500 mL). The mixture was extracted with EtOAc (3×300 mL) and the combined organic extracts were washed with brine (100 mL), then dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—100:0 to 50:50, to give the title compound. MS: m/z=351 (M+1).

1. stirringthe mixture was stirred at 0° C. for 1 h
2. stirringstirring
3. waitwas continued for 1 h
4. stirringThe reaction mixture was stirred for 1 h
5. customquenched with saturated aqueous NH4Cl (125 mL) and H2O (500 mL)
6. extractionThe mixture was extracted with EtOAc (3×300 mL)
7. washthe combined organic extracts were washed with brine (100 mL)
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude product was purified by silica gel chromatography
12. washeluting with a gradient of hexane