Methanol → Methyl 4-bromo-2-methylbenzoate

HRID 859733Notes

Reaction equation

HRID 859733 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([CH3:11])[CH:3]=1.S(=O)(=O)(O)O.[CH3:17]O>>[CH3:17][O:7][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([Br:1])=[CH:3][C:4]=1[CH3:11]

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 995704-Bromo-2-methylbenzoic acid

Product 1

HCID 22031226Methyl 4-bromo-2-methylbenzoateYield 87%

Procedure

To a solution of 4-bromo-2-methyl-benzoic acid 10.0 g, 46.5 mmol) in methanol (100 mL) at room temperature was added sulfuric acid (conc. 1 mL) dropwise. The solution was heated at reflux for 16 h. The solution was removed from heat and sulfuric acid (conc. 0.5 mL) was added. The solution was heated at reflux 2 h then cooled to room temperature and concentrated in vacuo. The residue was dissolved in ethyl acetate and washed with saturated sodium bicarbonate, then with saturated sodium chloride. The solution was dried (MgSO4), filtered, and concentrated in vacuo to a crude colorless oil. Flash chromatography (SiO2, 5% ethyl acetate/hexane) gave the title compound as a colorless oil (9.2 g, 87%). 1H NMR (400 MHz, CDCl3): δ ppm 2.58 (s, 3 H) 3.88 (s, 3 H) 7.38 (dd, J=8.46, 1.89 Hz, 1 H) 7.42 (d, J=1.52 Hz, 1 H) 7.78 (d, J=8.34 Hz, 1 H).

Workup

  1. temperatureThe solution was heated
  2. temperatureat reflux for 16 h
  3. customThe solution was removed
  4. temperaturefrom heat
  5. additionsulfuric acid (conc. 0.5 mL) was added
  6. temperatureThe solution was heated
  7. temperatureat reflux 2 h
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue was dissolved in ethyl acetate
  10. washwashed with saturated sodium bicarbonate
  11. dry with materialThe solution was dried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo to a crude colorless oil

Sources & evidence

ORD record
ord-24f6f5f28bdb407e8dfdf35631e4a6f7
Source dataset
uspto-grants-2006_12
Patent number
US07151105B2

Reaction notes

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