Water → 5-Bromo-3-fluoro-2-hydroxybenzaldehyde

HRID 2421579Notes

Reaction equation

HRID 2421579 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[CH:3]=1.[CH2:10]1N2CN3CN(C2)CN1C3.[OH2:20].S(=O)(=O)(O)O>FC(F)(F)C(O)=O>[Br:1][C:2]1[CH:3]=[C:4]([F:9])[C:5]([OH:8])=[C:6]([CH:7]=1)[CH:10]=[O:20]

Participants

6

Reactant 4

HCID 962WaterHCID 1118Sulfuric AcidHCID 4101HexamethylenetetramineHCID 27249814-Bromo-2-fluorophenol

Product 1

HCID 27792765-Bromo-3-fluoro-2-hydroxybenzaldehydeYield 43%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 4-bromo-2-fluorophenol (100 g, 0.52 mol) in trifluoroacetic acid (TFA) (400 mL) , hexamethylenetetramine (HMT) (146.8 g, 1.05 mol) was added under a nitrogen atmosphere in three portions over 20 minutes, the mixture was stirred at room temperature for 20 minutes, and then at 90° C. for 13 hours, and then cooled to room temperature. Water (600 mL) and a 50% aqueous solution of sulfuric acid (300 ML) were sequentially added thereto at room temperature, and the mixture was stirred at room temperature for two hours. The resultant mixture was extracted three times with ethyl acetate (1 L), the organic layer was washed four times with 1 N aqueous solution of hydrochloric acid (1 L), twice with saturated saline, and dried over anhydrous magnesium sulfate. The solvent was distilled off from the organic layer under reduced pressure and the residue was azeotroped twice with toluene. Ethanol (20 mL) was added to the residue, and the solid obtained after filtration of the suspended solution was washed twice with ethanol (10 mL) to give 49.6 g of the title compound (yield: 43%).

Workup

  1. waitat 90° C. for 13 hours
  2. temperaturecooled to room temperature
  3. stirringat room temperature, and the mixture was stirred at room temperature for two hours
  4. extractionThe resultant mixture was extracted three times with ethyl acetate (1 L)
  5. washthe organic layer was washed four times with 1 N aqueous solution of hydrochloric acid (1 L)
  6. dry with materialtwice with saturated saline, and dried over anhydrous magnesium sulfate
  7. distillationThe solvent was distilled off from the organic layer under reduced pressure
  8. customthe residue was azeotroped twice with toluene
  9. additionEthanol (20 mL) was added to the residue
  10. customthe solid obtained
  11. filtrationafter filtration of the suspended solution
  12. washwas washed twice with ethanol (10 mL)

Sources & evidence

ORD record
ord-ac64877a25e94f92b16c37d7bc948d47
Source dataset
uspto-grants-2011_06
Patent number
US07956222B2

Reaction notes

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