Chemical Properties
white to light yellow crystal
Uses
5-Bromo-2-hydroxynicotinic acid is used as an intermediate in the preparation of antihypertensive drugs, antiviral drugs, and antihistamines.
Synthesis
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)-.
References
[1] Patent: WO2004/110442, 2004, A1. Location in patent: Page 17; 18
[2] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 9, p. 2566 - 2569
[3] Patent: US2002/161000, 2002, A1
[4] Patent: US2006/287292, 2006, A1. Location in patent: Page/Page column 26
[5] Organic Process Research and Development, 2008, vol. 12, # 4, p. 603 - 613
