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

Participants

Reaction Steps

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−).

Provenance & Evidence