Synthesis
To an anhydrous tetrahydrofuran (THF, 20 mL) solution of 2-bromo-4-fluorobenzonitrile (5.0 g, 25.0 mmol) was slowly added isopropylmagnesium chloride (PrMgCl, 2.0 M solution of THF, 15.0 mL, 30.0 mmol) at -30 °C. The reaction temperature was maintained at -30°C with continuous stirring for 3 hours. Subsequently, N,N-dimethylformamide (DMF, 5.80 mL, 75.0 mmol) was added to the reaction system. The reaction mixture was gradually warmed to room temperature and stirring was continued for 1 hour. Upon completion of the reaction, the mixture was cooled to -10 °C, 2 M hydrochloric acid (37 mL) was slowly added and stirred at this temperature for 20 min. The reaction solution was concentrated in vacuum to 1/3 of the original volume and then extracted with ethyl acetate (EtOAc, 3 times). The organic phases were combined, dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated to give the target product 4-fluoro-2-formylbenzonitrile (3.9 g, 71% yield).
