Hydrochloric Acid → Methyl 6-[3-[(4-methoxybenzyl)oxy]-4-chlorophenyl]-5-hydroxypyridine-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of 80 g (345 mmol) of methyl 6-bromo-5-hydroxy-2-pyridine-carboxylate and 146 g (499 mmol) of [3-[(4-methoxybenzyl)oxy]-4-chloro-phenyl]boronic acid in 1600 mL of anhydrous dioxane is stirred for 15 minutes while sparging with argon, followed by addition of 143 g (1034 mmol) of anhydrous K2CO3 and 14 g (17.2 mmol) of PdCl2(dppf). The reaction medium is stirred for 10 hours at 95° C. under argon, cooled to room temperature and then poured at room temperature into 2 L of EtOAc and 350 mL of aqueous 1N HCl solution. The organic phase is washed with 300 mL of aqueous 1N HCl solution and 600 mL of water. After drying over Na2SO4 and concentrating under reduced pressure, the precipitate is taken up in 500 mL of a 7/3 pentane/DCM mixture, filtered and washed with 200 mL of pentane. 105 g of methyl 6-[3-[(4-methoxybenzyl)oxy]-4-chloro-phenyl]-5-hydroxypyridine-2-carboxylate are thus obtained in the form of a brown powder, which is used without further purification in the following step.

Provenance & Evidence