3-cyano-2,4-difluorobenzoic acid

Synthesis

To a 1 L reaction vial were sequentially added 49.9 g (0.36 mol) of 2,4-difluoro-3-carboxamide benzoic acid, 31.6 g (0.40 mol) pyridine, and 376 g tetrahydrofuran (THF). Place in a low temperature bath to cool down to -5 , dropwise addition of 83.2g (0.396mol) trifluoroacetic anhydride (TFAA), about 1h dropwise. The reaction was held at -5~5 for 1 h, then warmed up to 30 and held for 3 h. At the end of the reaction, desolventized to remove THF, added 100 g of water and 180 g of ethyl acetate, partitioned, washed with water, collected the organic phase, and removed the ethyl acetate to obtain 3-cyano-2,4-difluorobenzoic acid.