[Synthesis]
General procedure for the synthesis of 5-BOC-aminonicotinic acid from 2,5-pyridinedicarboxylic acid: (A) Preparation of 5-[(tert-butoxycarbonyl)amino]nicotinic acid: 2,5-pyridinedicarboxylic acid (5.00 g, 29.9 mmol) was suspended in tert-butanol (35 mL), and triethylamine (8.34 mL, 59.8 mmol) and diphenylphosphate azide ( 7.10 mL, 32.9 mmol), followed by heating the reaction mixture under reflux conditions for 3 hours. Upon completion of the reaction, it was cooled by an ice bath and the pH of the reaction mixture was adjusted to less than 10 by addition of 1N aqueous sodium hydroxide solution, followed by washing with ether. The reaction mixture was again cooled in an ice bath and the pH was adjusted with 1N aqueous sodium hydroxide solution to about 4. The precipitated solid was collected by filtration and washed sequentially with water and ether to give 5-BOC-aminonicotinic acid as a white powder (3.27 g, 45.9% yield).1H-NMR (DMSO-d6) δ: 1.49 (9H, s), 8.45 (1H, s ), 8.66 (1H, s), 8.75 (1H, s), 9.83 (1H, br). |