Peracetic Acid → 5-Hydroxy-2-methoxypyridine

Participants

Reaction Conditions

Reaction Steps

A 2.5 M hexane solution of n-butyllithium (23 mL, 58 mmol) was added over 30 minutes to a −78° C. solution of 5-bromo-2-methoxypyridine (10 g, 53 mmol) in ether (120 mL), keeping the temperature below −65° C. The slurry was stirred for 30 minutes, and then trimethylborate (6.1 mL) was added quickly to the reaction solution. Again the temperature was maintained below −65° C. The solution was stirred for 10 minutes, warmed to 15° C. and then cooled to −78° C. Peracetic acid (56 mmol) was added dropwise, while the temperature was kept at or below −65° C. After addition, the reaction was warmed briefly to −50° C., cooled back to −65° C., then stirred at approximately 25° C. overnight. The reaction was quenched with water (100 mL), and then extracted with ether (3×150 mL). The organic portions were combined and washed with aqueous NaHSO3 solution and brine. The organic portions were extracted two times with 2N aqueous NaOH solution. The pooled basic aqueous fractions were washed with Et2O and then acidified with NaHSO4. The product precipitated out as oil; the aqueous mixture was extracted three times with Et2O, the pooled ether fractions were dried with Na2SO4, and stripped of solvent in vacuo. Yielded 3.6 g of a brown solid.

Provenance & Evidence