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

HRID 705334Notes

Reaction equation

HRID 705334 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.C1(C)C=CC=CC=1.[C:23]1(=O)[CH:28]=[CH:27][C:26](=[O:29])[CH:25]=[CH:24]1>O1CCCC1.[Cl-].[Zn+2].[Cl-]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:15][C:23]3[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][C:24]=3[C:9]=2[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 1140TolueneHCID 4650QuinoneHCID 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 8028TetrahydrofuranSolvent

Procedure

The material prepared in Example 1A (250 g, 1.19 mole) was combined with zinc chloride (243.5 g, 1.784 mole) and toluene (3.75 L). The reaction mixture was heated to reflux under a nitrogen atmosphere. Benzoquinone (167 g, 1.546 mole) in tetrahydrofuran (500 mL) was added dropwise to the reaction, and upon completion of the addition, the reaction mixture was heated at reflux for 6 hours. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was concentrated in vacuo to a brown solid. The solid was recrystallized from acetonitrile yielding the title compound as a brown solid (125 g, 35%). MS m/z 301 (M+H)+.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux under a nitrogen atmosphere
  3. additionupon completion of the addition
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 6 hours
  6. customThe reaction mixture was quenched with water
  7. extractionextracted with ethyl acetate
  8. concentrationThe organic layer was concentrated in vacuo to a brown solid
  9. customThe solid was recrystallized from acetonitrile yielding the title compound as a brown solid (125 g, 35%)

Sources & evidence

ORD record
ord-4b9b4ec8eb144e82acbc16f296163900
Source dataset
uspto-grants-2015_11
Patent number
US09173887B2

Reaction notes

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