5-HYDROXY-2-METHOXYPYRIDINE

13472-85-0

51834-97-0

Step 2. Synthesis of 5-hydroxy-2-methoxypyridine: To a stirred solution of 5-bromo-2-methoxypyridine (8.9 g, 47.9 mmol) in tetrahydrofuran (THF, 175 mL) was added slowly and dropwise to a solution of n-butyllithium (2.5 M hexane solution, 28.7 mL, 71.8 mmol) at -78 °C. The reaction was continued for 45 min with stirring. The reaction mixture was stirred continuously at -78 °C for 45 min. Subsequently, trimethyl borate (7.06 mL, 62.2 mmol) was added via syringe and the mixture continued to be stirred at the same temperature for 2 hours. The reaction mixture was warmed up to 0 °C and treated by adding a mixture of 3N NaOH solution (25 mL, 71.77 mmol) and 30% hydrogen peroxide solution (~50 mL). The reaction mixture gradually turned yellow and slightly turbid and was then warmed to room temperature, held for 30 minutes and then heated to reflux temperature and maintained for 1 hour. After completion of the reaction, the mixture was cooled to room temperature. The aqueous layer was neutralized with 1N HCl solution and subsequently extracted with ether (Et2O, 2 x 100 mL). The organic layers were combined, dried with anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to give a yellow viscous oily product (3.5 g, 60% yield).