Ethyl Acetate → 2-(4-Hydroxy-2,3-dimethylphenyl)acetic acid

HRID 2423286Notes

Reaction equation

HRID 2423286 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10](N2CCCC2)=[O:11])=[C:5]([CH3:17])[C:4]=1[CH3:18].[OH-].[Na+].C(OCC)(=[O:23])C>Br.C(O)(=O)C>[OH:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:11])=[O:23])=[C:5]([CH3:17])[C:4]=1[CH3:18]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 598648482-(4-Methoxy-2,3-dimethylphenyl)-1-(pyrrolidin-1-yl)ethanone

Product 1

HCID 598647702-(4-Hydroxy-2,3-dimethylphenyl)acetic acid

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 260Hydrogen BromideSolvent

Procedure

2-(4-Methoxy-2,3-dimethylphenyl)-1-(pyrrolidin-1-yl)ethanone was suspended in a mixture of 48% HBr (aq) (15 mL) and acetic acid (15 mL) and the reaction was heated to reflux for 24 h. The reaction was poured over ice and brought to pH 4 with 1 N NaOH. Ethyl acetate was added and the layers were separated. The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The residue was taken up in dioxane (100 mL) and 1 N HCl (15 mL) was added. The reaction was heated to reflux for 4 days. Ethyl acetate and 1N HCl were added. The layers were separated, and the aqueous layer was washed with additional ethyl acetate. The organics were combined, dried (Na2SO4), filtered and concentrated in vacuo. Flash column chromatography of the residue, eluting 0% to 7% methanol in dichloromethane, afforded the title compound. LC-MS ESI (neg.) m/z: 179.2 (M−H).

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux for 24 h
  3. additionThe reaction was poured over ice
  4. customthe layers were separated
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. addition1 N HCl (15 mL) was added
  9. temperatureThe reaction was heated
  10. temperatureto reflux for 4 days
  11. additionEthyl acetate and 1N HCl were added
  12. customThe layers were separated
  13. washthe aqueous layer was washed with additional ethyl acetate
  14. dry with materialdried (Na2SO4)
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. washFlash column chromatography of the residue, eluting 0% to 7% methanol in dichloromethane

Sources & evidence

ORD record
ord-408a99575e6e4679be12f50f4a8700b4
Source dataset
uspto-grants-2011_06
Patent number
US07960567B2

Reaction notes

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