Ethanol → 2-Methyl-5-(3-pyridyl)-anisole

HRID 1269530Notes

Reaction equation

HRID 1269530 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]([CH3:10])=[C:6]([O:8][CH3:9])[CH:7]=1.C(B(CC)[C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1)C.C(=O)([O-])[O-].[Na+].[Na+].C(O)C>O1CCCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:10][C:5]1[CH:4]=[CH:3][C:2]([C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)=[CH:7][C:6]=1[O:8][CH3:9]

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 6428513-(Diethylboryl)pyridineHCID 108902465-Iodo-2-methyl anisole

Product 1

HCID 184484682-Methyl-5-(3-pyridyl)-anisoleYield 100%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

5-iodo-2-methyl anisole (9.60 g, 38.70 mmol) and diethyl-(3-pyridyl)borane (5.70 g, 38.70 mmol) were dissolved in 60 mL tetrahydrofuran in a 250 mL round bottom flask equipped with a magnetic stirrer. Sodium carbonate (8.20 g, 77.40 mmol) and 30 mL water were added followed by tetrakis(triphenylphosphine)palladium(0) (0.90 g, 0.77 mmol) and 15 mL ethanol. The mixture was heated at reflux for 24 h under nitrogen then cooled to ambient temperature. The mixture was diluted with 200 mL water and extracted with diethyl ether (2×200 mL). The organic phases were combined and extracted with 1N HCl (3×150 mL). The acidic extractions were combined and made basic with 5N aqueous sodium hydroxide. This basic layer was extracted with diethyl ether (3×150 mL) and the extracts were combined and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield 7.71 g (99%) of 2-methyl-5-(3-pyridyl)-anisole as a brown oil.

Workup

  1. customequipped with a magnetic stirrer
  2. temperatureThe mixture was heated
  3. temperatureat reflux for 24 h under nitrogen
  4. extractionextracted with diethyl ether (2×200 mL)
  5. extractionextracted with 1N HCl (3×150 mL)
  6. extractionThe acidic extractions
  7. extractionThis basic layer was extracted with diethyl ether (3×150 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-17a13958cb68414489a9fdf762665fa7
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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