Synthesis
General procedure for the synthesis of 2-fluoro-5-methoxyphenylacetonitrile from the compound (CAS: 773837-37-9) and 2-fluoro-5-methoxybenzyl bromide: Sodium cyanide (362 mg, 7.53 mmol) was added to a solution of compound 4 (1.5 g, 6.84 mmol) in anhydrous ethanol (15 mL), and the reaction mixture was stirred for 2 hr at 85 °C. The progress of the reaction was monitored by thin layer chromatography (TLC) and after confirming the complete consumption of the raw materials, the reaction mixture was concentrated to obtain the crude product. The crude product was diluted with ice water (30 mL) and extracted with ethyl acetate (2 x 50 mL). The organic layers were combined, washed with brine (20 mL), dried over anhydrous sodium sulfate and concentrated to give the residue. The residue was purified by rapid chromatography on silica gel (eluent: petroleum ether/ethyl acetate, gradient gradually increased from 100/0 to 70/30) to afford compound 5 (1 g, 90% yield) as a colorless liquid.1H NMR (400 MHz, DMSO-d6) δ: 7.21 (t, J = 9.2 Hz, 1H), 7.01 (dd, J = 6.1, 3.1 Hz, 1H), 6.94 (m, 1H), 4.01 (s, 2H), 3.75 (s, 3H). Mass spectrum (ESI) m/z: 166.06 [M+H]+.
