Dimethyl pyridine-2,6-carboxylate → Methyl 6-(hydroxymethyl)picolinate

A suspension of dimethyl 2,6-pyridine-dicarboxylate (100 g, 513 mmol) in methanol (800 mL) and tetrahydrofuran (300 mL) was heated to dissolve and while the solution was still hot, it was treated in portions with sodium borohydride (18.2 g, 479 mmol) over 1 hour. The mixture was stirred for 1 hour at room temperature, cooled to 0-5° C., and quenched with 10% citric acid (160 mL), stirred for another 15 minutes, and filtered. The filtrate was concentrated, dissolved in dichloromethane, dried (sodium sulfate), filtered, and concentrated to a white solid. The solid was heated to dissolve in ethyl acetate (100 mL), stirred for 16 hours at room temperature, filtered and concentrated to give the title compound (44.5 g, 56% yield). 1H NMR (CDCl3) δ ppm 3.50(s, 1H), 4.00 (s, 3 H), 4.86 (s, 2 H), 7.52 (d, 1 H), 7.85 (t, 1 H), 8.04 (d, 1 H).

1. temperaturewas heated
2. dissolutionto dissolve and while the solution
3. temperaturecooled to 0-5° C.
4. customquenched with 10% citric acid (160 mL)
5. stirringstirred for another 15 minutes
6. filtrationfiltered
7. concentrationThe filtrate was concentrated
8. dissolutiondissolved in dichloromethane
9. dry with materialdried (sodium sulfate)
10. filtrationfiltered
11. concentrationconcentrated to a white solid
12. temperatureThe solid was heated
13. dissolutionto dissolve in ethyl acetate (100 mL)
14. stirringstirred for 16 hours at room temperature
15. filtrationfiltered
16. concentrationconcentrated

ORD record

ord-18392a829c054434a7bfa1493843c477

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07834043B2