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

HRID 1770897Notes

Reaction equation

HRID 1770897 reaction equation
Br[C:2]1[C:7]([Br:8])=[CH:6][C:5]([Cl:9])=[CH:4][N:3]=1.[CH3:10]B(O)O.C([O-])([O-])=O.[K+].[K+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[Br:8][C:7]1[C:2]([CH3:10])=[N:3][CH:4]=[C:5]([Cl:9])[CH:6]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 139377Methylboronic Acid2×HCID 110001622,3-Dibromo-5-chloropyridine

Product 1

HCID 469118403-Bromo-5-chloro-2-methylpyridineYield 13%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

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, 0-20% 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, 3H), 8.29 (d, 1H), 8.52 (d, 1H); MS (CI) m/z 206 [M+H]+.

Workup

  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, 0-20% MeOH containing 0.1 M NH3 in DCM)
  15. additionThe fractions containing pure product
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-75498429856f4964b5ba956dca7e0d75
Source dataset
uspto-grants-2016_02
Patent number
US09248129B2

Reaction notes

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