Ethyl bromoacetate → (+/-)-Ethyl (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 (3.00 g, 16.8 mmol, described in Intermediate 17) in DMF (100 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil; 740 mg, 18.5 mmol) and the resulting mixture was stirred for 30 min. Ethyl bromoacetate (1.87 mL, 16.8 mmol) in DMF (10 mL) was added dropwise over 10 min. The reaction mixture was stirred at 0° C. for 2 h, then quenched with H2O (200 mL). The mixture was extracted with EtOAc (5×200 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, followed by crystallization from hexane:EtOAc to give the title compound. MS: m/z=265 (M+1).

1. stirringThe reaction mixture was stirred at 0° C. for 2 h
2. customquenched with H2O (200 mL)
3. extractionThe mixture was extracted with EtOAc (5×200 mL)
4. washthe combined organic extracts were washed with brine (100 mL)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude product was purified by silica gel chromatography
9. washeluting with a gradient of hexane
10. customEtOAc—100:0 to 0:100, followed by crystallization from hexane

ORD record

ord-cabd5e95a22a4d789ee3a92e9c00100f

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07947677B2