Acetic Acid → 4-(4-Hydroxyphenyl)-3-methyl-4-oxo-butyric acid ethyl ester

HRID 887043Notes

Reaction equation

HRID 887043 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH:6]([CH3:17])[C:7]([C:9]1[CH:14]=[CH:13][C:12]([O:15]C)=[CH:11][CH:10]=1)=[O:8])[CH3:2].C(O)(=O)C.Br>C(O)C>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH:6]([CH3:17])[C:7]([C:9]1[CH:10]=[CH:11][C:12]([OH:15])=[CH:13][CH:14]=1)=[O:8])[CH3:2]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 260Hydrogen BromideHCID 148665764-(4-Methoxy-phenyl)-3-methyl-4-oxo-butyric acid ethyl ester

Product 1

HCID 596519524-(4-Hydroxyphenyl)-3-methyl-4-oxo-butyric acid ethyl esterYield 45.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of crude 4-(4-methoxy-phenyl)-3-methyl-4-oxo-butyric acid ethyl ester (44 g, 175.8 mmol), acetic acid (300 mL) and 48% aqueous HBr (150 mL) was stirred at reflux for 10 h. The reaction was cooled to rt, concentrated at reduced pressure then partitioned between methylene chloride and water and the aqueous layer was extracted three times with methylene chloride and concentrated to provide a crude material. The crude material was dissolved in ethanol (125 mL) and added amberlyst then heated at 85° C. for 15 h. The reaction mixture was filtered over celite at rt and the filtrate was concentrated at reduced pressure and then partitioned between water and methylene chloride. The aqueous layer was extracted twice with methylene chloride to furnish a crude product and the crude product was purified by ISCO (330 g silica gel column) chromatography using 20 to 30% EtOAc in hexane to obtain a mixture (19 g) of 4-(4-hydroxyphenyl)-3-methyl-4-oxo-butyric acid ethyl ester (MS m/z 235 (M−H) and p-hydroxypropiophenone. The mixture was used for the next reaction without further purification.

Workup

  1. temperatureat reflux for 10 h
  2. concentrationconcentrated at reduced pressure
  3. customthen partitioned between methylene chloride and water
  4. extractionthe aqueous layer was extracted three times with methylene chloride
  5. concentrationconcentrated
  6. customto provide a crude material
  7. additionadded
  8. temperatureamberlyst then heated at 85° C. for 15 h
  9. filtrationThe reaction mixture was filtered over celite at rt
  10. concentrationthe filtrate was concentrated at reduced pressure
  11. custompartitioned between water and methylene chloride
  12. extractionThe aqueous layer was extracted twice with methylene chloride
  13. customto furnish a crude product
  14. customthe crude product was purified by ISCO (330 g silica gel column) chromatography

Sources & evidence

ORD record
ord-5bd9a20672ff4b279b5517fed9502ad8
Source dataset
uspto-grants-2012_08
Patent number
US08247414B2

Reaction notes

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