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

HRID 1839614Notes

Reaction equation

HRID 1839614 reaction equation
[F:1][C:2]([F:20])([F:19])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:11]=2[CH:12]=[CH:13][NH:14]3)=[CH:6][CH:5]=1.[Br-].[Br-].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.C(O)(=[O:44])C>CC(O)(C)C.C(O)C.C(O)(=O)C.[Zn]>[F:20][C:2]([F:1])([F:19])[O:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:11]=2[CH2:12][C:13](=[O:44])[NH:14]3)=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 21124087PyridiniumtribromideHCID 225618044-(4-trifluoromethoxy-phenyl)-1H-indole

Product 1

HCID 225617784-(4-Trifluoromethoxy-phenyl)-1,3-dihydro-indol-2-oneYield 39%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 86587657t-BuOH ethanol aceticacidSolvent

Conditions

Temperature
27 °C

Procedure

To the suspension of 4-(4-trifluoromethoxy-phenyl)-1H-indole (4.93 g, 17.78 mmol) in t-BuOH-ethanol-acetic acid (3:2:1) (261 mL) was added pyridinium tribromide (17.06 g, 53.34 mmol)) portionwise. The mixture was stirred at 27° C. for 3 hours, and then to the mixture was added acetic acid (105 mL). Zinc dust was added to the reaction mixture portionwise until the color changed from deep red to light yellow, and the reaction mixture was stirred at room temperature for one hour. The unreacted zinc dust was filtered off and washed with ethanol. The filtrate was concentrated, and the syrupy residue was dissolved in ethyl acetate, which was washed with water, 0.5 N HCl, sat. NaHCO3 and brine, and dried over Na2SO4. After filtration and evaporation, the crude product was triturated with diethyl ether to provide product 4-(4-trifluoromethoxy-phenyl)-1,3-dihydro-indol-2-one (2.05 g, 39%) as a tan solid.

Workup

  1. stirringwas stirred at room temperature for one hour
  2. filtrationThe unreacted zinc dust was filtered off
  3. washwashed with ethanol
  4. concentrationThe filtrate was concentrated
  5. dissolutionthe syrupy residue was dissolved in ethyl acetate
  6. washwhich was washed with water, 0.5 N HCl, sat. NaHCO3 and brine
  7. dry with materialdried over Na2SO4
  8. filtrationAfter filtration and evaporation
  9. customthe crude product was triturated with diethyl ether

Sources & evidence

ORD record
ord-f292fb373c9d4ccf9b7fbd34140966bd
Source dataset
uspto-grants-2004_01
Patent number
US06677368B2

Reaction notes

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