Hydrochloric Acid → 3,5-Difluoro-4-hydroxybenzaldehyde

Participants

Reaction Steps

A solution of 2,6-difluorophenol (5.00 g, 38.43 mmol) and hexamethylenetetramine (HMTA) (5.93 g, 42.30 mmol) in trifluoroacetic acid (TFA) (50 ml) was heated under reflux 16 h. The reaction mixture was cooled to room temperature, poured on to HCl (150 ml 4 M) and stirred for 3 hours and brought to pH 3 via the addition of NaOH solution (5 M). The organic phase was extracted in to diethyl ether (4×100 ml), the combined ethereal extracts dried (MgSO4) and the solvent removed in vacuo. The residue were purified by column chromatography [silica gel, eluted with hexane:EtOAc, 4:1] providing white solid (6.1 g, 38 mmol, 99%).

Provenance & Evidence