Toluene → 5-Methyl-2-phenylpyridine

HRID 2369743Notes

Reaction equation

HRID 2369743 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.[C:9]1(B(O)O)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=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.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>[CH3:8][C:5]1[CH:6]=[CH:7][C:2]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:3][CH:4]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 66827Phenylboronic AcidHCID 5642162-Bromo-5-methylpyridineHCID 22031701Potassium phosphate, tribasic, monohydrate

Product 1

HCID 474675-Methyl-2-phenylpyridineYield 88.3%

Reagents, catalysts & solvents 3

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

Procedure

2-Bromo-5-methylpyridine (30 g, 174 mmol), phenylboronic acid (25.5 g, 209 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (2.86 g, 6.98 mmol) and potassium phosphate tribasic monohydrate (120 g, 523 mmol) were added to toluene (600 mL) and water (60 mL). The reaction mixture was degassed with nitrogen for 20 min. Pd2(dba)3 (3.19 g, 3.49 mmol) was added and the reaction mixture was refluxed for 18 h. After cooling, the organic layer was separated and the aqueous layer extracted with 3×50 mL dichloromethane, dried over sodium sulfate and evaporated. The crude product was chromatographed on silica gel with 75/25 (v/v) hexane/EtOAc and then distilled on a Kugelrohr apparatus (150° C., 100 mbar) to give 26 g (88%) of 5-methyl-2-phenylpyridine as a white solid. The product was confirmed by NMR and GC/MS. HPLC purity: 99.2%.

Workup

  1. customThe reaction mixture was degassed with nitrogen for 20 min
  2. temperaturethe reaction mixture was refluxed for 18 h
  3. temperatureAfter cooling
  4. customthe organic layer was separated
  5. extractionthe aqueous layer extracted with 3×50 mL dichloromethane
  6. dry with materialdried over sodium sulfate
  7. customevaporated
  8. customThe crude product was chromatographed on silica gel with 75/25 (v/v) hexane/EtOAc
  9. distillationdistilled on a Kugelrohr apparatus (150° C., 100 mbar)

Sources & evidence

ORD record
ord-ea3aaf6a7a174f4c9a6d983a235140d5
Source dataset
uspto-grants-2014_04
Patent number
US08709615B2

Reaction notes

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