Cu(TFA)2 (20 mmol) was added to a pressure-sealed tube containing 0.75 mL of DMSO with 4-fluoro-3-methoxyphenylacetic acid (0.5 mmol) and urea (1.5 mmol). The reaction system was oxygenated and stirred at 130 °C for about 20 h. The reaction process was monitored by TLC and GC (the exact reaction time was determined based on GC and TLC monitoring results). Upon completion of the reaction, the reaction was cooled to room temperature. To the reaction mixture, 20 mL of ethyl acetate was added and washed sequentially with NaHCO3 solution (20 mL x 2) and water. The organic phases were combined and dried over anhydrous sodium sulfate. The aqueous phase was then extracted with ethyl acetate (20 mL x 2) and all organic phases were combined. The solvent was removed by rotary evaporator to obtain the crude product. The crude product was purified by silica gel column chromatography with the eluent ratio of ethyl acetate:petroleum ether=50:1. 4-fluoro-3-methoxybenzonitrile was finally obtained in 84% yield.
