Toluene → 2,5-Diphenyl-4-ethylpyridine

HRID 1897977Notes

Reaction equation

HRID 1897977 reaction equation
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:11]1[CH:16]=[C:15]([CH2:17][CH3:18])[C:14](I)=[CH:13][N:12]=1.[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]([CH2:17][CH3:18])[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 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 582007282-Chloro-4-ethyl-5-iodopyridine

Product 1

HCID 584350442,5-Diphenyl-4-ethylpyridineYield 90.9%

Reagents, catalysts & solvents 3

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

Procedure

Phenylboronic acid (11.0 g, 90 mmol), 2-chloro-4-ethyl-5-iodopyridine (8.00 g, 30 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (492 mg, 1.2 mmol), and potassium phosphate tribasic (20.7 g, 90 mmol), 250 ml, of toluene and 25 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) (275 mg, 0.3 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 from the aqueous layer. The organic layer was washed with saturated brine solution and dried over magnesium sulfate. The solution was filtered and the solvent was removed under vacuum to give a off-white solid. This crude was purified by silica gel column chromatography eluting with 10% ethyl acetate/hexanes. 7.0 g of desired product was obtained after purification (90.9% 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. temperaturewas cooled
  6. customthe organic layer was separated from the aqueous layer
  7. washThe organic layer was washed with 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 off-white solid
  12. customThis crude was purified by silica gel column chromatography
  13. washeluting with 10% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-afc643553f3143d19b431b6b4132882f
Source dataset
uspto-grants-2013_08
Patent number
US08519384B2

Reaction notes

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