Toluene → 4-Methyl-2,5-diphenylpyridine

HRID 1897974Notes

Reaction equation

HRID 1897974 reaction equation
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:11]1[CH:16]=[C:15]([CH3:17])[C:14](Br)=[CH:13][N:12]=1.O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[C:28]1(C)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.O>[C:1]1([C:11]2[CH:16]=[C:15]([CH3:17])[C:14]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:13][N:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 66827Phenylboronic AcidHCID 27344292,5-Dibromo-4-methylpyridineHCID 22031701Potassium phosphate, tribasic, monohydrate

Product 1

HCID 149249864-Methyl-2,5-diphenylpyridineYield 87.2%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 962WaterSolvent

Procedure

Phenylboronic acid (72.9 g, 598 mmol), 2,5-dibromo-4-methylpyridine (50 g, 199 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (3.3 g, 8 mmol), potassium phosphate tribasic monohydrate (137 g, 595 mmol), 650 mL of toluene and 150 mL of water were placed in a 2 L round-bottom flask. Nitrogen was bubbled directly into the reaction mixture for 30 min after which tris(dibenzylideneacetone)dipalladium(0) (1.79 g, 1.96 mmol) was added. Nitrogen was bubbled into the reaction mixture for another 15 min before the reaction mixture was heated to reflux for 16 h under nitrogen. After the reaction was completed the mixture was cooled and the organic layer was separated from the aqueous layer. The organic layer was washed with a saturated brine solution and then dried over magnesium sulfate. The solution was filtered, and the solvent was removed under vacuum to give a yellow solid as the crude. The crude was purified by column chromatography using silica gel as the stationary phase and 10% ethyl acetate in hexanes as the mobile phase. The product was further purified by recrystallization from hexanes. 42.6 g of desired product was obtained after purification (87.2% yield).

Workup

  1. additionwas added
  2. customNitrogen was bubbled into the reaction mixture for another 15 min before the reaction mixture
  3. temperaturewas heated
  4. temperatureto reflux for 16 h under nitrogen
  5. temperaturewas cooled
  6. customthe organic layer was separated from the aqueous layer
  7. washThe organic layer was washed with a saturated brine solution
  8. dry with materialdried over magnesium sulfate
  9. filtrationThe solution was filtered
  10. customthe solvent was removed under vacuum
  11. customto give a yellow solid as the crude
  12. customThe crude was purified by column chromatography
  13. customThe product was further purified by recrystallization from hexanes

Sources & evidence

ORD record
ord-70cc753660be46acb40763f614c170f3
Source dataset
uspto-grants-2013_08
Patent number
US08519384B2

Reaction notes

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