Toluene → 5-Methyl-2-phenylpyridine

HRID 713564

Reaction equation

HRID 713564 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-3696a75dda6f4de794b2f810fe82a3af
Source dataset
uspto-grants-2015_11
Patent number
US09184397B2

Linked notes

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