Triphenylphosphine → 5-Bromo-3,3'-bipyridine

HRID 2209336Notes

Reaction equation

HRID 2209336 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[N:9]1[CH:14]=[CH:13][CH:12]=[C:11](B(O)O)[CH:10]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1.O>[Br:8][C:6]1[CH:7]=[C:2]([C:11]2[CH:10]=[N:9][CH:14]=[CH:13][CH:12]=2)[CH:3]=[N:4][CH:5]=1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 62657Potassium Phosphate, TribasicHCID 693693,5-DibromopyridineHCID 27343783-Pyridinylboronic acid

Product 1

HCID 135464585-Bromo-3,3'-bipyridineYield 48%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Compound 6 (see WO2009/009756) was prepared as follows: a mixture of 3,5-dibromopyridine (10.6 g, 44.7 mmol), pyridin-3-ylboronic acid (5.50 g, 44.7 mmol), palladium(II) acetate (0.550 g, 2.45 mmol), triphenylphosphine (2.50 g, 9.53 mmol), potassium phosphate tribasic (19.0 g, 89.5 mmol), H2O (45 mL) and 1,4-dioxane (200 mL) was degassed with argon for 2 h. while stirring. The reaction mixture was then maintained under argon at reflux (120° C.) while stirring for 1.5 h. Upon confirming consumption of the starting material by TLC (SiO2, 7:3 dichloromethane-acetone), the reaction was cooled to RT and poured over ethyl acetate (about 400 mL). The organic phase was then washed with saturated NaHCO3, H2O and brine, dried over MgSO4, filter and concentrated in vacuo. The crude product was purified via flash chromatography (SiO2, 4:1 dichloromethane-acetone) to provide Compound 6 (5.03 g, 48%) as a white solid.

Workup

  1. customCompound 6 (see WO2009/009756) was prepared
  2. customwas degassed with argon for 2 h.
  3. temperatureThe reaction mixture was then maintained under argon
  4. stirringwhile stirring for 1.5 h
  5. customconsumption of the starting material by TLC (SiO2, 7:3 dichloromethane-acetone)
  6. temperaturethe reaction was cooled to RT
  7. additionpoured over ethyl acetate (about 400 mL)
  8. washThe organic phase was then washed with saturated NaHCO3, H2O and brine
  9. dry with materialdried over MgSO4
  10. filtrationfilter
  11. concentrationconcentrated in vacuo
  12. customThe crude product was purified via flash chromatography (SiO2, 4:1 dichloromethane-acetone)

Sources & evidence

ORD record
ord-f399446e4b9a42a090790d50d9e8ba6a
Source dataset
uspto-grants-2016_06
Patent number
US09379336B2

Reaction notes

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