Methyl iodide → (-)-Ethyl (3-methyl-4-nitro-2-oxo-2,3-dihydro-1H-indol-3-yl)acetate

To a stirred solution of 4-nitro-1,3-dihydro-2H-indol-2-one (6.95 g, 39.0 mmol, described in Intermediate 44) in DMF (180 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil; 1.72 g, 42.9 mmol) and the resulting mixture was stirred for 30 min. Iodomethane (2.43 mL, 39.0 mmol) in DMF (20 mL) was added dropwise over 20 min, and the mixture was stirred at 0° C. for 1 h. A further equivalent of sodium hydride (60% dispersion in mineral oil; 1.56 g, 39.0 mmol) was added and stirring was continued for 1 h. Ethyl bromoacetate (3.46 mL, 31.2 mmol) in DMF (20 mL) was added dropwise over 20 min. The reaction mixture was stirred at 0° C. for 1 h, then quenched with saturated aqueous NH4Cl (500 mL). The mixture was extracted with EtOAc (3×500 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 0:100, to give the title compound. MS: m/z=279 (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 at 0° C. for 1 h
5. customquenched with saturated aqueous NH4Cl (500 mL)
6. extractionThe mixture was extracted with EtOAc (3×500 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

ORD record

ord-6e1e835d627a44d4b36528974e09e7df

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07696192B2