Methyl 6-methoxypyridine-3-carboxylate → (6-Methoxypyridin-3-yl)methanol

Participants

Reaction Steps

A solution of methyl 6-methoxy-nicotinate (50 mmol) in anhydrous methanol (60 mL) was treated with sodium borohydride (122 mmol) at 0° C., warmed to ambient temperature for 18 h, then heated to reflux for 6 h. The incomplete reaction product was concentrated to dryness in vacuo, dissolved in anhydrous 1,4-dioxane (70 mL), treated with more sodium borohydride (122 mmol), and heated to reflux for 18 h. After cooling to ambient temperature, the reaction was quenched with methanol, filtered over a coarse glass frit, solids washed with methanol, and the filtrate concentrated. The residue was repeatedly dissolved in methanol, filtered, and concentrated in vacuo until no solids remained, then triturated with 10% MeOH/CH2Cl2, filtered, and concentrated. The impure product was then adsorbed onto silica gel, poured onto a 9.5×5.5 cm plug of silica gel, and eluted with a gradient of 0 to 15% MeOH/CHCl3, and the pure fractions concentrated in vacuo giving the title compound as a pale yellow oil. 1H NMR (CDCl3) δ 8.08 (1H, d, J=2.5 Hz), 7.61 (1H, dd, J=8.5 Hz, 2.4 Hz), 6.74 (1H, d, J=8.5 Hz), 4.60 (2H, s), 3.92 (3H, s).

Provenance & Evidence