Acetic Acid → Methyl 5-hydroxynaphthalene-2-carboxylate

HRID 1385305Notes

Reaction equation

HRID 1385305 reaction equation
C[O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[CH:6][C:7]([C:13]([OH:15])=[O:14])=[CH:8]2.Br.[C:17](O)(=O)C>>[OH:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[CH:6][C:7]([C:13]([O:15][CH3:17])=[O:14])=[CH:8]2

Participants

4

Reactant 3

HCID 176Acetic AcidHCID 260Hydrogen BromideHCID 129927605-Methoxy-2-naphthoic acid

Product 1

HCID 18520031Methyl 5-hydroxynaphthalene-2-carboxylate

Procedure

5-Methoxy-2-naphthoic acid (49.7 g, 0.246 mol, J. Med. Chem. 1993, 36, 2485) in glacial acetic acid (450 ml) and in 48% strength aqueous hydrobromic acid solution (450 ml) is heated to reflux for 15 h. After cooling, the reaction mixture is concentrated in vacuo and is extracted with dichloromethiane after addition to water. The orgoanic phase is washed with water, dried over MgSO4 and concentrated in vacuo. The residue is dissolved in MeOH (1.6 1). The solution is saturated with hydrogen chloride (about 1 h), the reaction mixture heating to reflux temperature. The solvent is then stripped off in vacuo, the residue is taken up in ethyl acetate, and the mixture is washed with satd NaCl solution, dried (MgSO4) and concentrated in vacuo. The residue is chromatographed on silica gel using dichloromethane:ethyl acetate (20:1). The product thus obtained is stirred with dichloromethane/petroleum ether, filtered off with suction and dried in vacuo.

Workup

  1. temperatureto reflux for 15 h
  2. temperatureAfter cooling
  3. concentrationthe reaction mixture is concentrated in vacuo
  4. extractionis extracted with dichloromethiane
  5. additionafter addition to water
  6. washThe orgoanic phase is washed with water
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue is dissolved in MeOH (1.6 1)
  10. customis saturated with hydrogen chloride (about 1 h)
  11. temperaturethe reaction mixture heating
  12. temperatureto reflux temperature
  13. washthe mixture is washed with satd NaCl solution
  14. dry with materialdried (MgSO4)
  15. concentrationconcentrated in vacuo
  16. customThe residue is chromatographed on silica gel
  17. customThe product thus obtained
  18. filtrationfiltered off with suction
  19. customdried in vacuo

Sources & evidence

ORD record
ord-1fe872c834934c7ea8e867dd873a012c
Source dataset
uspto-grants-2001_07
Patent number
US06262112B1

Reaction notes

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