The general procedure for the synthesis of 2-fluoro-4-methoxybenzaldehyde from pyridine trioxide and 2-fluoro-4-methoxybenzyl alcohol was as follows: triethylamine (0.92 mL, 6.60 mmol) was added to a solution of 2-fluoro-4-methoxybenzyl alcohol (346.9 mg, 2.22 mmol) in DMSO (8 mL). Subsequently, pyridine sulfur trioxide (1.0501 g, 6.60 mmol) was added to the mixture in batches and the change in reaction temperature was monitored. The reaction mixture was stirred for 0.5 hours. After completion of the reaction, the mixture was poured into 5% aqueous KHSO4 solution and extracted three times with ethyl acetate, the organic layers were combined and dried over anhydrous MgSO4. The organic layer was concentrated under reduced pressure and the resulting crude product was purified by silica gel column chromatography (eluent: hexane/ether=5/1) to afford the target compound 2-fluoro-4-methoxybenzaldehyde (301 mg, 88% yield). The product was characterized by 1H-NMR (CDCl3): δ 10.21 (s, 1H), 7.83 (t, 1H, J=8.3 Hz), 6.79 (ddd, 1H, J=8.3, 2.3, 0.7 Hz), 6.65 (dd, 1H, J=12.2, 2.3 Hz), 3.88 (s, 3H).
