General procedure for the synthesis of 6-bromo-3-hydroxypyridine-2-carboxylic acid from 3-hydroxy-2-pyridinecarboxylic acid: to a stirred suspension of 3-hydroxypyridine-2-carboxylic acid (2.00 g, 0.0144 mol) in DMF (30 mL) was slowly added a solution of N-bromosuccinimide (2.56 g, 0.0144 mol) in DMF (30 mL). After 1 h of reaction, water (50 mL) and 1 M NaOH aqueous solution (25 mL) were added, followed by extraction of the reaction mixture with chloroform (3 x 150 mL). The organic layers were combined and concentrated under reduced pressure and the resulting residue was purified by preparative HPLC (System D). The final product 6-bromo-3-hydroxypyridine-2-carboxylic acid was obtained as 366 mg in 12% yield. The product was assayed by analytical HPLC and the purity was 100% in both cases (System A and B); LRESIMS (ESI+) m/z = 218/220 (M + H)+.
