General procedure for the synthesis of 3-fluoro-4-methylbenzonitrile from methyl 2-(4-cyano-2-fluorophenyl)acetate: 1.0 g of methyl 2-(4-cyano-2-fluorophenyl)acetate was added to a 50 mL four-necked flask, followed by the addition of 0.19 g of water, 1.15 g of 95% anhydrous calcium chloride and 15 g of N,N-dimethylacetamide. The mixture was stirred and heated to 140°C to 145°C and the reaction was carried out for 20 to 24 hours (the progress of the reaction was monitored by HPLC to ensure >99% conversion). Upon completion of the reaction, the mixture was cooled to 60°C to 70°C and subsequently concentrated under reduced pressure. Finally, the product was purified by column chromatography to afford 0.62 g of 3-fluoro-4-methylbenzonitrile as a light yellow solid in 89.0% yield.
