Hydrochloric Acid → 1-Methyl-6-oxo-1,6-dihydropyridine-3-boronic Acid

Temperature

90 °C

5-Bromo-1-methylpyridin-2(1H)-one (400 mg, 2.17 mmol), tricyclohexylphosphine (72 mg, 0.26 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (540 mg, 2.17 mmol), potassium acetate (522 mg, 5.32 mmol) and Pd2(dba)3 (97 mg, 0.11 mmol) were added to a flask. The flask was evacuated and purged with argon three times. Fully degassed dioxane (9.5 mL) was added and the reaction was sealed and heated at 90° C. overnight. The mixture was then cooled to room temperature, filtered over a thin layer of celite, eluting with dichloromethane. The majority of the dichloromethane was evaporated under reduced pressure and hexane was added until a precipitate formed. The slurry was filtered and the filtrate was concentrated. The resulting residue was dissolved in dioxane, 10 equivalents of 1 N hydrochloric acid were added, and the mixture was stirred overnight. Removal of the solvent under reduced pressure and purification of the resulting residue via reverse phase HPLC (10-100% acetonitrile/water+0.05% TFA modifier) afforded the title compound.

1. customThe flask was evacuated
2. custompurged with argon three times
3. additionFully degassed dioxane (9.5 mL) was added
4. customthe reaction was sealed
5. temperatureThe mixture was then cooled to room temperature
6. filtrationfiltered over a thin layer of celite,
7. washeluting with dichloromethane
8. customThe majority of the dichloromethane was evaporated under reduced pressure and hexane
9. additionwas added until a precipitate
10. customformed
11. filtrationThe slurry was filtered
12. concentrationthe filtrate was concentrated
13. dissolutionThe resulting residue was dissolved in dioxane
14. customRemoval of the solvent
15. customunder reduced pressure and purification of the resulting residue via reverse phase HPLC (10-100% acetonitrile/water+0.05% TFA modifier)

ORD record

ord-2d6f90f1d77d484cbd87362308b2ec98

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08367706B2