Hydrochloric Acid → 4-Fluoro-2-hydroxybenzaldehyde

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).

1. customwas removed by distillation at 80° C
2. additionAdditional benzene (50 ml) was added to the reaction
3. temperatureAfter heating
4. temperatureat reflux for 3 hours
5. temperatureto cool to room temperature
6. customthe organic layer was separated
7. washwashed with H2O
8. dry with materialAfter drying over MgSO4
9. customthe solvent was removed under reduced pressure
10. customThe resulting residue was purified by flash chromatography

ORD record

ord-181d57e23e8f4d86b4e5d685e0a7fe14

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07741326B2