Sodium Sulfite → 1-Acetyl-6-bromo-5-fluoro-2-methylindolin-3-one

HRID 331050Notes

Reaction equation

C([O:4][C:5]1[C:13]2[C:8](=[CH:9][C:10]([Br:15])=[C:11]([F:14])[CH:12]=2)[N:7]([C:16](=[O:18])[CH3:17])[C:6]=1[CH3:19])(=O)C.S([O-])([O-])=O.[Na+].[Na+]>C(O)C.O>[C:16]([N:7]1[C:8]2[C:13](=[CH:12][C:11]([F:14])=[C:10]([Br:15])[CH:9]=2)[C:5](=[O:4])[CH:6]1[CH3:19])(=[O:18])[CH3:17]

Participants

Conditions

Temperature: 110 °C

Procedure

To a mixture of 1-acetyl-6-bromo-5-fluoro-2-methyl-1H-indol-3-yl acetate (D87) (1.22 g, 3.72 mmol) in ethanol (15 mL) was added a solution of sodium sulfite (0.562 g, 4.46 mmol) in water (15.00 mL). The mixture was then heated at 110° C. for 2 hours. After cooling to RT, ethanol was removed under reduced pressure. The aqueous residue was poured into water (50 mL) and extracted with DCM (20 mL×3). The organic layers were combined, washed with brine (100 mL), filtered through phase separator and evaporated in vacuo. The crude residue was purified by chromatography on silica, eluting with a gradient of 0-40% ethyl acetate in cyclohexane to give title compound (769.5 mg). LCMS (A): m/z (M+H)+ 286/288, C11H9BrFNO2 requires 285/287 (acidic).

Workup

temperatureAfter cooling to RT
customethanol was removed under reduced pressure
additionThe aqueous residue was poured into water (50 mL)
extractionextracted with DCM (20 mL×3)
washwashed with brine (100 mL)
filtrationfiltered through phase separator
customevaporated in vacuo
customThe crude residue was purified by chromatography on silica
washeluting with a gradient of 0-40% ethyl acetate in cyclohexane

Sources & evidence

ORD record: ord-29ae4acd40884071af62152824cdec8b
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08877742B2

Reaction notes

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