At 0°C, 2 M i-PrMgCl THF (2.2 ml, 1.0 equivalent) solution was added over 5 minutes to an anhydrous THF (20 ml) solution of 3-bromo-2-hydroxypyridine (0.76 g, 4.4 mmol, 1.0 equivalent). The clear solution was stirred at this temperature for another 5 minutes, and a 2.5 M hexane solution of n-butyllithium (3.5 ml, 2.0 equivalent) was added dropwise over 5 minutes while maintaining the temperature below -20°C. The resulting mixture was stirred at this temperature for 0.5 hours, and dried CO2 (0.20 g, 1.0 equivalent) was added to the -20°C system. The resulting mixture was heated to -20°C over 0.5 hours and quenched with water (6 ml). After stirring the mixture below -20°C for 10 minutes, the phases were separated, and the aqueous phase was extracted once more with ethyl acetate. The resulting suspension was brought to room temperature and passed through a 0.5 × 1 cm silica gel sieve, eluted with 10 ml of ethyl acetate. The filtrate was concentrated, and the residue was purified by rapid silica gel chromatography (eluent: petroleum ether/ethyl acetate = 10:1) to give the product 2-hydroxynicotinic acid, a grayish-white solid, 0.48 g (yield: 79%), mp: 255–257°C.
