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

HRID 2305403Notes

Reaction equation

HRID 2305403 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 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 Merck silica gel 60 (70-230 mesh) with 85:5:5:0.5 hexane/chloroform/ethyl acetate/methanol/aqueous ammonia.

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-b266ce1d5b7c401c95dbb319697eaef5
Source dataset
uspto-grants-2002_08
Patent number
US06440970B1

Reaction notes

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