C([O:3][C:4](=[O:18])[C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:7][CH:6]=1)C.CO.O.O[Li].O>C1COCC1>[C:12]1([NH:11][C:8]2[CH:9]=[CH:10][C:5]([C:4]([OH:18])=[O:3])=[CH:6][N:7]=2)[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1A mixture of 6-chloronicotinic acid ethyl ester (0.2 g, 0.00108 mole) and aniline (0.119 g, 0.00129 mole) in ethoxyethanol (10 mL) was heated to reflux for overnight. The mixture was then concentrated under reduced pressure and the residue was dissolved in ethyl acetate. The organic layer was washed with water, brine solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography using silica gel 60-120 mesh (5% ethyl acetate in hexane) to afford 0.23 g (88%) of 6-phenylamino-nicotinic acid ethyl ester. To a stirred solution 6-phenylamino-nicotinic acid ethyl ester (0.23 g, 0.00095 mol) in a mixture of THF (4 mL), methanol (4 mL) and H2O (2 mL) was added LiOH.H2O (0.159 g, 0.0038 mol) at ambient temperature and the resulting mixture was stirred overnight. Volatiles were then evaporated and the resulting residue was diluted with water, acidified with 10% aqueous citric acid solution. The resulting precipitate was isolated by filtration and dried to afford 0.174 g (85%) of 6-Phenylamino-nicotinic acid.
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