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

HRID 2272274Notes

Reaction equation

HRID 2272274 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([C:6]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:7])=[CH:4][CH:3]=1.[C:16]1(=O)[CH:21]=[CH:20][C:19](=[O:22])[CH:18]=[CH:17]1>C(O)C.CC(OC)(C)C.[Cl-].[Zn+2].[Cl-]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]2[O:7][C:16]3[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][C:17]=3[C:8]=2[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:14][CH:15]=1

Participants

6

Reactant 2

HCID 4650QuinoneHCID 101336Ethyl 3-(4-chlorophenyl)-3-oxopropanoate

Product 1

HCID 46172351Ethyl 2-(4-chlorophenyl)-5-hydroxy-1-benzofuran-3-carboxylateYield 44%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 702EthanolSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
95 °C

Procedure

Zinc chloride (28.3 g, 0.207 mol) was stirred in anhydrous ethanol (45 mL) then heated to 95° C. (reflux) under nitrogen atmosphere using oven dried glassware. Ethyl 4-chlorobenzoylacetate (44 g, 0.194 mol) was added as a single portion followed by dropwise addition of a solution of benzoquinone (22.6 g, 0.21 mol) in anhydrous MTBE (500 mL) over 2 hours. This was performed with a simultaneous distillation of MTBE from the reaction mixture such that the reaction volume remained approximately constant. A bath temperature of 145-155° C. and an internal temperature of 75-95° C. maintained throughout most of the addition. Halfway through the addition more anhydrous ethanol (45 mL) was added because the reaction mixture became thick and a loss of some of the original volume of ethanol through the distillation was suspected. After addition was complete, heating continued for 30 minutes. The reaction mixture was cooled to room temperature and partitioned between water (100 mL) and EtOAc (250 mL). The insoluble solids were removed by filtration of the biphasic solution and the organic layer was then separated, washed with more water, dried and evaporated under vacuum. The residual brown solid was slurried in warm dichloromethane and the mixture cooled to room temperature and cooled further by refrigeration overnight. The tan solid was filtered from the dark brown solution and washed with a small volume of DCM and dried under vacuum to give ethyl 2-(4-chlorophenyl)-5-hydroxybenzofuran-3-carboxylate (27 g, 44%).

Workup

  1. temperature(reflux) under nitrogen atmosphere
  2. customdried glassware
  3. distillationThis was performed with a simultaneous distillation of MTBE from the reaction mixture such that the reaction volume
  4. temperatureA bath temperature of 145-155° C. and an internal temperature of 75-95° C. maintained throughout
  5. additionmost of the addition
  6. additionHalfway through the addition more anhydrous ethanol (45 mL)
  7. additionwas added because the reaction mixture
  8. distillationa loss of some of the original volume of ethanol through the distillation
  9. additionAfter addition
  10. temperatureheating
  11. temperatureThe reaction mixture was cooled to room temperature
  12. custompartitioned between water (100 mL) and EtOAc (250 mL)
  13. customThe insoluble solids were removed by filtration of the biphasic solution
  14. customthe organic layer was then separated
  15. washwashed with more water
  16. customdried
  17. customevaporated under vacuum
  18. temperaturethe mixture cooled to room temperature
  19. temperaturecooled further by refrigeration overnight
  20. filtrationThe tan solid was filtered from the dark brown solution
  21. washwashed with a small volume of DCM
  22. customdried under vacuum

Sources & evidence

ORD record
ord-b72fb89a139a4cceb58fa6977c9b594e
Source dataset
uspto-grants-2015_09
Patent number
US09119868B2

Reaction notes

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