Dimethylformamide → 2-Fluoro-3-phenoxybenzaldehyde

Participants

Reaction Conditions

Reaction Steps

Cool a solution of 2,2,6,6-tetramethylpiperidine (5.1 mL, 30.0 mmol) in THF (40 mL) to −78° C. Add dropwise n-Butyllithium (18.7 mL, 30.0 mmol, 1.6M in hexanes) and stir for 10 min at −78° C. Add dropwise 2-fluorophenyl phenyl ether (4.7 g, 25.0 mmol), stir 2 h at −78° C. Add N,N-dimethylformamide (2.3 mL, 30.0 mmol) dropwise over 15 min. Stir the resulting mixture for 3 h at −78° C. and allow to warm to ambient temperature over 16 h. Quench the reaction mixture with water (50 mL), extract with ethyl acetate, dry over Na2SO4, filter and concentrate under reduced pressure to give an oil. Crystallize the oil with hexanes to give a solid, collect and recrystallize from hexanes/ethyl acetate/methylene chloride to give the title compound: mp 75-77° C.; MS (m/e): 216 (M+); Calculated for C13H9FO2: Calcd: C, 72.22; H, 4.20. Found: C, 72.41; H, 4.23. Purification of the mother liquors by silica gel chromatography (2-3% ethyl acetate/hexanes) gives an additional amount of the title compound: MS (m/e): 216 (M+).

Provenance & Evidence