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

HRID 2354461Notes

Reaction equation

HRID 2354461 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1.Br[C:13]1[CH:14]=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=1.[OH-].[Na+]>CN(C=O)C.O>[Br:19][C:17]1[CH:16]=[N:15][CH:14]=[C:13]([O:11][C:8]2[CH:9]=[CH:10][C:5]([O:4][CH3:3])=[CH:6][CH:7]=2)[CH:18]=1

Participants

7

Reactant 4

HCID 90154-MethoxyphenolHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 693693,5-Dibromopyridine

Product 1

HCID 120162263-Bromo-5-(4-methoxyphenoxy)pyridineYield 120.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred suspension of sodium hydride (3.0 g of 80% in mineral oil, 100 mmol) in DMF (95 mL) in an ice water bath, 4-methoxyphenol (12.2 g, 96 mmol) was added slowly under a nitrogen atmosphere. The resulting mixture was warmed to ambient temperature and stirred for 1 h. 3,5-Dibromopyridine (15.6 g of 98%, 65 mmol) was added and the mixture was then heated at 85° C. (bath temperature) for 32 h. The mixture was cooled, diluted with water (120 mL), poured into 5N sodium hydroxide (15 mL), and extracted with ether (3×150 mL). The combined ether extracts were dried (Na2SO4), filtered and concentrated by rotary evaporation, to give a light-yellow oil (21.9 g). The oil was diluted with ethanol and rotary evaporated (twice) to remove residual DMF and then diluted with ether (50 mL) and suction filtered to remove un-reacted 3,5-dibromopyridine. Rotary evaporation and high vacuum treatment left a lard-like product weighing 12.8 g. The product was 94% pure by GC-MS analysis (66% yield) and was sometimes used, without further purification, in subsequent reactions. When desired, further purification (to 99.4%) was accomplished by column chromatography on silica gel, using 85:5:5:4.5:0.5 hexane/chloroform/ethyl acetate/methanol/aqueous ammonia as eluent.

Workup

  1. temperaturethe mixture was then heated at 85° C. (bath temperature) for 32 h
  2. temperatureThe mixture was cooled
  3. extractionextracted with ether (3×150 mL)
  4. dry with materialThe combined ether extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-1a2c3b59e822468b8af28e3ddceaf32e
Source dataset
uspto-grants-2010_07
Patent number
USRE041439E1

Reaction notes

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