Acetic Acid → 4-(2,3-Difluoro-phenyl)-1,3-dihydro-indol-2-one

HRID 1839629Notes

Reaction equation

HRID 1839629 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[CH:12][NH:13]2.C([OH:20])C.C(O)(=O)C.[Br-].[Br-].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>CC(O)(C)C.[Zn]>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH2:11][C:12](=[O:20])[NH:13]2

Participants

7

Reactant 4

HCID 176Acetic Acid2×HCID 702EthanolHCID 21124087PyridiniumtribromideHCID 22561761HCID 22561761, compound

Product 1

HCID 225619714-(2,3-Difluoro-phenyl)-1,3-dihydro-indol-2-oneYield 76%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 6386tert-ButanolSolvent

Procedure

To the suspension of 4-(2,3-difluoro-phenyl)-1H-indole (2.85 g, 12.4 mmol) in t-BuOH:ethanol:acetic acid (78.5 mL:46.5 mL:24.13 mL) was added pyridinium tribromide (11.93 g, 37.3 mmol) portionwise. The mixture was stirred at room temperature for 3 hours, and then to the mixture was added with acetic acid (60 mL). Zinc dust (4.1 g, 62.2 mmol) was added to the reaction mixture portionwise. After stirring for one hour, any unreacted zinc was filtered off and most of the solvent was removed under reduced pressure. The residue was diluted with ethyl acetate, washed with water (5×), sat NaHCO3, brine, dried over Na2SO4, concentrated and triturated with ether to give 2.32 g (76%) of 4-(2,3-difluoro-phenyl)-1,3-dihydro-indol-2-one as an earth colored solid.

Workup

  1. stirringAfter stirring for one hour
  2. filtrationany unreacted zinc was filtered off and most of the solvent
  3. customwas removed under reduced pressure
  4. additionThe residue was diluted with ethyl acetate
  5. washwashed with water (5×)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customtriturated with ether

Sources & evidence

ORD record
ord-2f200598a07347f782b6e0a11a70414f
Source dataset
uspto-grants-2004_01
Patent number
US06677368B2

Reaction notes

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