Hexamethylenetetramine → 4-Hydroxy-3-methoxy-5-(trifluoromethyl)benzaldehyde

HRID 62777Notes

Reaction equation

HRID 62777 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([C:9]([F:12])([F:11])[F:10])[C:4]=1[OH:13].C1N2CN3CN(C2)CN1C3.[C:24](O)(C(F)(F)F)=[O:25]>>[OH:13][C:4]1[C:5]([C:9]([F:11])([F:10])[F:12])=[CH:6][C:7]([CH:24]=[O:25])=[CH:8][C:3]=1[O:2][CH3:1]

Participants

4

Reactant 3

HCID 4101HexamethylenetetramineHCID 6422Trifluoroacetic acidHCID 151333362-Methoxy-6-(trifluoromethyl)phenol

Product 1

HCID 193891994-Hydroxy-3-methoxy-5-(trifluoromethyl)benzaldehydeYield 34%

Procedure

A mixture of 2-methoxy-6-(trifluoromethyl)phenol (2) (2.5 g, 13 mmol) and hexamethylenetetramine (1.8 g, 13 mmol) in TFA (40 mL) was stirred under reflux for 3 h. The solvent was removed in vacuo and the residue was dissolved in 1M HCl (20 mL). The product was extracted with DCM (3×20 mL), the combined organics were washed with brine (2×20 mL) and then the solvent was removed in vacuo. The residue was purified by silica gel chromatography (80 g, 0-100% EtOAc in isohexane) to afford 4-hydroxy-3-methoxy-5-(trifluoromethyl)benzaldehyde (3) (1.03 g, 34%) as a white solid: m/z 219 [M−H]− (ES−).

Workup

  1. temperatureunder reflux for 3 h
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in 1M HCl (20 mL)
  4. extractionThe product was extracted with DCM (3×20 mL)
  5. washthe combined organics were washed with brine (2×20 mL)
  6. customthe solvent was removed in vacuo
  7. customThe residue was purified by silica gel chromatography (80 g, 0-100% EtOAc in isohexane)

Sources & evidence

ORD record
ord-6cab4cb58ef2417f882db86d17ad2986
Source dataset
uspto-grants-2016_09
Patent number
US09447028B2

Reaction notes

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