3-FLUORO-5-FORMYLBENZONITRILE CAS 1003708-42-6 C8H4FNO

General procedure for the synthesis of 3-fluoro-5-formylbenzonitrile from N,N-dimethylformamide and 3-bromo-5-fluorobenzonitrile: Dissolve 3-bromo-5-fluorobenzonitrile (5.00 g, 25.0 mmol) in anhydrous THF (25 mL) and cool to 0°C. Over a period of 5 minutes, add a pre-chilled THF solution of 2 M isopropylmagnesium chloride (iPrMgCl, 15.0 mL, 30.0 mmol) dropwise to the solution. Stir the reaction mixture at 0 °C for 15 minutes, then continue stirring at room temperature for 1 hour. The mixture was cooled again to 0 °C, and anhydrous DMF (5.81 mL, 75.0 mmol) was added. The mixture was stirred for 17 hours, during which time it was allowed to reach room temperature after 2 hours. The reaction mixture was poured into a mixture of ice-cold water (150 mL) and diethyl ether (Et₂O, 100 mL). The two-phase mixture was stirred, and the aqueous phase was adjusted to pH 3 with 6 M hydrochloric acid. Separate the organic layer; extract the aqueous layer with diethyl ether (2 × 100 mL). Combine the diethyl ether extracts, wash with saturated sodium chloride solution, and dry over magnesium sulfate and activated carbon. The dried solution was filtered through a silica gel plug and eluted with diethyl ether. The filtrate was concentrated to afford 3-fluoro-5-formylbenzonitrile, a yellow solid, with a yield of 3.68 g after vacuum drying (99% yield). ¹H NMR (CDCl₃) δ 10.0 (s, 1H), 8.00 (s, 1H), 7.81–7.86 (m, 1H), 7.62–7.67 (m, 1H).