Hydrochloric Acid → 4-Fluoro-2-hydroxybenzaldehyde

Participants

Reaction Steps

To a solution of 3-fluorophenol (1 ml, 11 mmol) in THF (20 ml) in a three-neck flask was added ethylmagnesium bromide (5.5 ml, 5.5 mmol, 1M in THF). After stirring at room temperature for 2 hours, benzene was added to the reaction mixture and THF was removed by distillation at 80° C. Additional benzene (50 ml) was added to the reaction, followed by NEt3 (2.3 ml, 16.5 mmol) and paraformaldehyde (1 g, 33.3 mmol). After heating at reflux for 3 hours, the reaction mixture was allowed to cool to room temperature and was poured into 250 ml of 10% HCl. EtOAc was added and the organic layer was separated and washed with H2O. After drying over MgSO4, the solvent was removed under reduced pressure. The resulting residue was purified by flash chromatography to give 4-fluoro-2-hydroxy-benzaldehyde as a white solid (560 mg, 36%), 1H NMR (CDCl3, 300 MHz) δ: 6.71 (m, 2H), 7.56 (dd, 1H, J=6.3 Hz, 8.6 Hz), 9.84 (s, 1H), 11.36 (s, 1H).

Provenance & Evidence