2-cyano-5-fluorobenzylbroMide

147754-12-9

421552-12-7

General procedure for the synthesis of 2-cyano-5-fluorobenzyl bromide from 4-fluoro-2-methylbenzonitrile: 1.35 g (10 mmol) of 4-fluoro-2-methylbenzonitrile was dissolved in 20 mL of carbon tetrachloride, and 0.25 g (0.015 mmol) of p-toluenesulfonic acid and 2.15 g (12 mmol) of N-bromosuccinimide (NBS) were added. The reaction mixture was heated and refluxed for 4 h. After completion of the reaction, it was cooled to room temperature and filtered. The organic layer was separated by adding 20 mL of saturated ammonium chloride solution to the filtrate. The organic layer was washed three times sequentially with 20 mL of water and 20 mL of saturated sodium chloride solution, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to remove the solvent. The crude product was purified by column chromatography (eluent: petroleum ether/ethyl acetate=3:1) to afford 2-bromomethyl-4-fluorobenzonitrile in 86% yield. 1.0 mmol of 2-bromomethyl-4-fluorobenzonitrile and 1.2 mmol of p-toluidine were dissolved in 50 mL of tetrahydrofuran and refluxed under stirring by heating to 60 °C. The mixture was then purified by the method. 0.2 g (3.0 mmol) of sodium ethoxide was added in batches and the reaction was continued at reflux for 8 hours. The progress of the reaction was monitored by thin layer chromatography (TLC). Upon completion of the reaction, it was cooled to room temperature and concentrated under reduced pressure. 20 mL of ethyl acetate was added, washed three times sequentially with 20 mL of water and 20 mL of saturated sodium chloride solution, the organic layer was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to remove the solvent. The crude product was purified by column chromatography (eluent: petroleum ether/ethyl acetate=10:1) to afford the intermediate compound 2-(p-methylphenylamino)methyl-4-fluorobenzonitrile in 95% yield. Mass spectrum (ESI+): m/z=241.4 (M+H)+.