Quinone → Ethyl 2-(4-fluorophenyl)-5-hydroxy-1-benzofuran-3-carboxylate

HRID 1671981Notes

Reaction equation

HRID 1671981 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:15])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.[C:16]1(=O)[CH:21]=[CH:20][C:19](=[O:22])[CH:18]=[CH:17]1.CCOC(C)=O>C1(C)C=CC=CC=1.[Cl-].[Zn+2].[Cl-]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:15][C:16]3[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][C:17]=3[C:9]=2[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 4650QuinoneHCID 8857Ethyl AcetateHCID 2758844Ethyl 3-(4-Fluorophenyl)-3-Oxopropanoate

Product 1

HCID 56604952Ethyl 2-(4-fluorophenyl)-5-hydroxy-1-benzofuran-3-carboxylate

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of zinc chloride (8.39 g, 1.14 mmol, 1 eq) in toluene at ambient temperature, ethyl 3-(4-fluorophenyl)-3-oxopropanoate (13 g, 2.74 mmol, 1 eq) was added and stirred at 70° C. for 15 min. Benzoquinone (6.66 g, 0.72 mmol, 1 eq) was added portion wise into the reaction mixture and stirred at the same temperature for 15-20 min. Dean-stark apparatus was assembled and the reaction mixture was heated at 140° C. for 12 h and cooled to ambient temperature. Reaction completion was judged by TLC. EtOAc was added to the reaction mass and filtered through the filter paper, to remove the inorganic material. Brine was added to the reaction mixture (filtrate) and extracted, dried over sodium sulphate and concentrated to get the crude material. Further it was purified by column chromatography using 10% EtOAc/Hexane system. Yield: 8.0 g (43%). 1H NMR (400 MHz, CDCl3): δ 1.38-1.42 (t, 3H, J=7.14 Hz), 4.37-4.42 (q, 2H, J=7.13 Hz), 5.2 (br s, 1H), 6.87-6.9 (q, 1H, J=3.81 Hz), 7.14-7.18 (q, 2H, J=5.82 Hz), 7.36-7.39 (d, 1H, J=8.80 Hz), 7.50-7.51 (d, 1H, J=2.56 Hz), 8.00-8.03 (m, 2H). LCMS: (ES+) m/z=301 (M+H).

Workup

  1. stirringstirred at the same temperature for 15-20 min
  2. temperaturethe reaction mixture was heated at 140° C. for 12 h
  3. temperaturecooled to ambient temperature
  4. customReaction completion
  5. filtrationfiltered through the filter paper
  6. customto remove the inorganic material
  7. additionBrine was added to the reaction mixture (filtrate)
  8. extractionextracted
  9. dry with materialdried over sodium sulphate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-5318f4816c2049c3bd9e8a0da9801770
Source dataset
uspto-grants-2011_08
Patent number
US07994171B2

Reaction notes

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