Sulfuric Acid → Ethyl (5-bromobenzofuran)-2-carboxylate

HRID 1836953Notes

Reaction equation

HRID 1836953 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][C:8]=1[CH:14]=O)[CH3:2].[O-]CC.[Na+].S(=O)(=O)(O)O.[OH-].[Na+]>CCO>[Br:13][C:10]1[CH:11]=[CH:12][C:7]2[O:6][C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:16])=[CH:14][C:8]=2[CH:9]=1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 880259ethyl (4-bromo-2-formylphenoxy)acetateHCID 2723922Sodium ethoxide

Product 1

HCID 735184Ethyl (5-bromobenzofuran)-2-carboxylateYield 27.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

The compound was prepared according to a literature procedure. (Yoo et al., Bioorg. Med. Chem. 5:445, 1997). To ethyl (4-bromo-2-formylphenoxy)acetate (Example 1, 14.3 g, 49.7 mmol) was added, under Ar, 115 mL absolute EtOH. To this mixture was added 5.28 g (77.7 mmol) sodium ethoxide and the reaction allowed to reflux overnight. Sulfuric acid (conc., 2 mL) was then added, and the reaction allowed to reflux an additional 2 hours. The mixture was then cooled to rt, 50 mL was added and the pH adjusted to neutrality with 1 N NaOH. The mixture was then extracted with 150 mL EtOAc, and the combined organic phase was washed with brine (2×150 mL), dried over Na2SO4, and filtered. The solvent was removed in vacuo. Purification by Biotage® separation using 5% EtOAc/hexanes provided 3.62 g (27%) of the desired compound. 1H-NMR (CDCl3, 67 ): 1.43 (t, 3H), 4.45 (q, 2H), 7.46-7.57 (m, 3H), 7.82 (s, 1H); LRMS (GC/MS/EI) 268 [M]+.

Workup

  1. customThe compound was prepared
  2. temperatureto reflux overnight
  3. temperatureto reflux an additional 2 hours
  4. addition50 mL was added
  5. extractionThe mixture was then extracted with 150 mL EtOAc
  6. washthe combined organic phase was washed with brine (2×150 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customThe solvent was removed in vacuo
  10. customPurification
  11. customby Biotage® separation

Sources & evidence

ORD record
ord-1cbcdac8127143b79bf00ffc4c7b03f6
Source dataset
uspto-grants-2004_08
Patent number
US06780859B2

Reaction notes

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