104612-36-4

609-71-2

104612-36-4

General procedure for the synthesis of 5-bromopyridine-3-carboxylic acid-2-one from 2-hydroxynicotinic acid: the compound was prepared according to the method of Y.S. Lo (Synthetic Communications, 1989, 553). Bromine (0.77 eq.) was slowly added dropwise to a stirred solution of 50% NaOH (2.4 eq.) in water (1 M solution) at 0 °C. After 5 min, 50% NaOH (3 eq.) was appended to the mixture, followed by the addition of solid 2-hydroxynicotinic acid (1 eq.) and the resultant solution was stirred continuously at 50 °C. After 20 h, a mixture of bromine ( 0.38 eq.) and a pre-prepared solution of 50% NaOH (1.2 eq.) in water (1 M solution) and continued stirring at 50 °C for 24 hours. Upon completion of the reaction, the mixture was cooled to 0 °C and acidified to pH 2 with concentrated hydrochloric acid to precipitate the solid product. The solid was separated by filtration, washed sequentially with warm water/isopropanol (3:1) and ether, and dried to give 5-bromo-2-hydroxynicotinic acid in 87% yield as an off-white solid. The product characterization data were as follows: 1H NMR (400 MHz, DMSO) δ 8.25 (1H, d, J = 2.7 Hz), 8.33 (1H, d, J = 2.7 Hz), 13.84 (2H, bs); 13C NMR (400 MHz, DMSO) δ 99.45, 117.97, 142.01, 147.42, 163.22, 163.88; MS (ES-) m/z 218-216 (M-H)-.