Toluene → 2-Methyl-3,6-diphenylpyridine

HRID 1897978Notes

Reaction equation

HRID 1897978 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]=[CH:15][C:14](Br)=[C:13]([CH3:18])[N:12]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[C:27]1(C)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=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]=[CH:15][C:14]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[C:13]([CH3:18])[N:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 27629463,6-Dibromo-2-methylpyridine

Product 1

HCID 214811592-Methyl-3,6-diphenylpyridineYield 92.7%

Reagents, catalysts & solvents 3

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

Procedure

Phenylboronic acid (24.3 g, 199.25 mmol), 2,5-dibromo-6-methylpyridine (10 g, 39.85 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (654 mg, 1.5 mmol), and potassium phosphate tribasic (27.5 g, 119.5 mmol), 300 mL of toluene and 30 mL of water were placed in a 1 L round-bottom flask. Nitrogen was bubbled directly into the mixture for 30 min after which tris(dibenzylideneacetone)dipalladium(0) (364 mg, 0.398 mmol) was added. Nitrogen was bubbled for another 15 min then 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. The organic layer was washed with a saturated brine solution and dried over magnesium sulfate. The solution was filtered and the solvent removed under vacuum. The crude was purified by column chromatography using silica gel as the stationary phase and 10%-20% ethyl acetate in hexanes as the mobile phase. 9.0 g of desired product was obtained after purification (92.7% yield)

Workup

  1. additionwas added
  2. customNitrogen was bubbled for another 15 min
  3. temperaturethe reaction mixture was heated
  4. temperatureto reflux for 16 h under nitrogen
  5. temperaturethe mixture was cooled
  6. customthe organic layer was separated
  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 removed under vacuum
  11. customThe crude was purified by column chromatography

Sources & evidence

ORD record
ord-2abfe1cd0ddc4d25b09e7df2390b8506
Source dataset
uspto-grants-2013_08
Patent number
US08519384B2

Reaction notes

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