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

A solution of methyl6-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).

1. temperatureheated
2. temperatureto reflux for 6 h
3. concentrationThe incomplete reaction product was concentrated to dryness in vacuo
4. dissolutiondissolved in anhydrous 1,4-dioxane (70 mL)
5. temperatureheated
6. temperatureto reflux for 18 h
7. temperatureAfter cooling to ambient temperature
8. customthe reaction was quenched with methanol
9. filtrationfiltered over a coarse glass frit, solids
10. washwashed with methanol
11. concentrationthe filtrate concentrated
12. dissolutionThe residue was repeatedly dissolved in methanol
13. filtrationfiltered
14. concentrationconcentrated in vacuo until no solids
15. customtriturated with 10% MeOH/CH2Cl2
16. filtrationfiltered
17. concentrationconcentrated
18. additionpoured onto a 9.5×5.5 cm plug of silica gel
19. washeluted with a gradient of 0 to 15% MeOH/CHCl3
20. concentrationthe pure fractions concentrated in vacuo

ORD record

ord-f2759c222261411788c3c7e5c1b0a542

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08030305B2