Water → 3-Bromo-5-(4-methoxyphenoxy)pyridine

HRID 2212136Notes

Reaction equation

HRID 2212136 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.[H-].[Na+].Br[C:13]1[CH:14]=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=1.O>CN(C)C=O.C(OCC)(=O)C>[Br:19][C:17]1[CH:16]=[N:15][CH:14]=[C:13]([O:9][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[CH:18]=1

Participants

7

Reactant 4

HCID 962WaterHCID 90154-MethoxyphenolHCID 24758Sodium hydrideHCID 693693,5-Dibromopyridine

Product 1

HCID 120162263-Bromo-5-(4-methoxyphenoxy)pyridineYield 96.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

Under an argon atmosphere, a solution of 4-methoxyphenol (15.7 g, 0.126 mol) in dimethylformamide (50 mL) was added slowly to a stirred suspension sodium hydride (3.6 g of a 80% suspension in mineral oil, 0.125 mol) in dimethylformamide (100 mL) at 3–7° C. The ice-bath was removed and the resulting mixture was stirred for 2 h at room temperature. A solution of 3,5-dibromopyridine (20 g, 0.083 mol) in dimethylformamide (120 mL) was added to the mixture, which was then heated to 100° C. for 36 h, then cooled to room temperature and poured into a mixture of water (500 mL) and ethyl acetate (500 mL). The aqueous phase was separated and extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with water (3×100 mL) and then brine (100 mL), then dried (MgSO4), filtered and concentrated by rotary evaporation to give 22.5 g of an orange oil, which was purified by column chromatography, with cyclohexane/ethyl acetate (95/5, v/v) as eluant. Selected fractions containing the product were concentrated via rotary evaporation to give 18.8 g (81%) of a colorless oil.

Workup

  1. customThe ice-bath was removed
  2. temperaturewas then heated to 100° C. for 36 h
  3. temperaturecooled to room temperature
  4. customThe aqueous phase was separated
  5. extractionextracted with ethyl acetate (2×100 mL)
  6. washThe combined organic phases were washed with water (3×100 mL)
  7. dry with materialbrine (100 mL), then dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-6a662fa96aa4413cb87766841fa5bae4
Source dataset
uspto-grants-2006_09
Patent number
US07101896B2

Reaction notes

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