Water → 5-Phenylamino-pyridine-2-carboxylic acid

A mixture of BINAP (0.167 g, 0.00027 mole), palladium acetate (0.06 g, 0.00027 mole) and toluene (10 mL) was degassed with argon for 15 minutes. This mixture was then added to a mixture of aniline (0.5 g, 0.00537 mole), 3-chloro-6-cyanopyridine (0.893 g, 0.00645 mole) and cesium carbonate (3.49 g, 0.01075 mole) in toluene (10 mL). The resulting mixture was heated to reflux for 22 hours. The reaction mixture was then concentrated under reduced pressure and the residue was extracted with ethyl acetate. The ethyl acetate layer was washed with water, brine solution, dried over sodium sulfate and concentrated under reduced pressure. Purification of the residue by column chromatography using silica gel 60-120 mesh (15% ethyl acetate in hexane) afforded 0.4 g (38%) of 5-phenylamino-pyridine-2-carbonitrile. To a stirred solution of 5-phenylamino-pyridine-2-carbonitrile (0.4 g, 0.00205 mol) in EtOH (15 mL) was added NaOH (0.246 g, 0.0061 mol) and water (10 mL) and the resulting mixture was heated to reflux for 4 hours. The mixture was then concentrated under reduced pressure and the residue was diluted with cold water. The resulting precipitate was isolated by filtration and dried to afford 0.385 g (87%) of 5-phenylamino-pyridine-2-carboxylic acid