Potassium Carbonate → 3-Bromo-5-chloro-2-methylpyridine

Temperature

50 °C

2,3-Dibromo-5-chloropyridine (1.3 g, 4.70 mmol), methylboronic acid (0.30 g, 5.01 mmol), bis(triphenylphosphine)palladium(II) chloride (0.50 g, 0.70 mmol) and dioxane (10 mL) were added. K2CO3 (2 M aq. solution, 7.0 mL, 14.0 mmol) was added and the reaction was put under N2 (g) atmosphere. The reaction was heated to reflux for 5 h. The reaction was stirred at 50° C. overnight and then heated to reflux for additionally 1 h. Methylboronic acid (0.14 g, 2.35 mmol) was added and the reaction was refluxed for 4 h and the allowed to cool down to r.t. The mixture was filtered through a silica plug. EtOAc and water were added and the phases were separated. The organic phase was washed two more times with water. The organic phase was dried with MgSO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (12 g SiO2, O-20% MeOH containing 0.1 M NH3 in DCM). The fractions containing pure product were pooled and concentrated, yielding the title compound (123 mg, 13% yield): 1H NMR (DMSO-d6) δ ppm 2.56 (s, 3 H), 8.29 (d, 1 H), 8.52 (d, 1 H); MS (CI) m/z 206 [M+H]+.

1. temperatureThe reaction was heated
2. temperatureto reflux for 5 h
3. temperatureheated
4. temperatureto reflux for additionally 1 h
5. temperaturethe reaction was refluxed for 4 h
6. temperatureto cool down to r.t
7. filtrationThe mixture was filtered through a silica plug
8. additionEtOAc and water were added
9. customthe phases were separated
10. washThe organic phase was washed two more times with water
11. dry with materialThe organic phase was dried with MgSO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customThe crude product was purified by flash chromatography (12 g SiO2
15. additionThe fractions containing pure product
16. concentrationconcentrated

ORD record

ord-b8063f7b0542437e99ada2ec5641aee2

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08865911B2