Chlorotrimethylsilane → 3-(Hydroxymethyl)pyridin-2(1H)-one

To a solution of 2-hydroxynicotinic acid (3-067-01) (5.0 g) in toluene (70 mL), and to the reaction mixture were added hexamethyldisilazane (HMDS, 19 mL) and chlorotrimethylsilane (TMSCl, 0.23 mL), and the reaction mixture was heated under reflux. After stirring for 2 h, the solvent was removed, and toluene was added to the residue. To the reaction mixture was added diisobutylaluminium hydride (DIBAL, 2 M toluene solution, 90 mL) at −78° C., after stirring for 4 h, the reaction was quenched with methanol. The insoluble substance was filtered off on Celite, and the filtrate was evaporated under reduced pressure. To the residue were added water and ethyl acetate, and the organic layer was separated, and then the aqueous layer was extracted with three times with ethyl acetate. The combined organic layers were washed with water, brine, dried over anhydrous magnesium sulfate, and evaporated to give 3-hydroxymethyl-2(11)-pyridone (7-008-01) (2.6 g, 59%) as a white solid.

1. temperaturethe reaction mixture was heated
2. temperatureunder reflux
3. customthe solvent was removed
4. additiontoluene was added to the residue
5. additionTo the reaction mixture was added diisobutylaluminium hydride (DIBAL, 2 M toluene solution, 90 mL) at −78° C.
6. stirringafter stirring for 4 h
7. customthe reaction was quenched with methanol
8. filtrationThe insoluble substance was filtered off on Celite
9. customthe filtrate was evaporated under reduced pressure
10. additionTo the residue were added water and ethyl acetate
11. customthe organic layer was separated
12. extractionthe aqueous layer was extracted with three times with ethyl acetate
13. washThe combined organic layers were washed with water, brine
14. dry with materialdried over anhydrous magnesium sulfate
15. customevaporated

ORD record

ord-c1d6e6131cce49d6843b5c9f9e705112

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07652141B2