Phenol → 3-Bromo-5-phenoxypyridine

HRID 2076407Notes

Reaction equation

HRID 2076407 reaction equation
[H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Br:10][C:11]1[CH:12]=[N:13][CH:14]=[C:15](Br)[CH:16]=1.[OH-].[Na+]>CN(C=O)C.O>[Br:10][C:11]1[CH:12]=[N:13][CH:14]=[C:15]([O:9][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[CH:16]=1

Participants

7

Reactant 4

HCID 996PhenolHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 693693,5-Dibromopyridine

Product 1

HCID 232635923-Bromo-5-phenoxypyridineYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (1.35 g of 80% in mineral oil, 45.0 mmol) was added to a stirred solution of phenol (4.26 g, 45.3 mmol) in DMF (30 mL) at 0° C., under nitrogen. The mixture was stirred at room temperature for 3 h, treated with 3,5-dibromopyridine (4.0 g, 16.9 mmol) and heated at 100° C. for 48 h. The reaction mixture was cooled to room temperature, poured into a mixture of water (100 mL) and 5M sodium hydroxide (10 mL), and extracted with ether (3×60 mL). The combined ether extracts were dried (Na2SO4), filtered, and rotary evaporated to a pale yellow semi-solid (4.9 g). This was chromatographed on a silica gel (200 g) column with hexane/ethyl acetate/chloroform (8:1:1, v/v) as eluent to give 2.86 g (68% yield) of a colorless oil.

Workup

  1. temperatureheated at 100° C. for 48 h
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionextracted with ether (3×60 mL)
  4. dry with materialThe combined ether extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. customrotary evaporated to a pale yellow semi-solid (4.9 g)
  7. customThis was chromatographed on a silica gel (200 g) column with hexane/ethyl acetate/chloroform (8:1:1

Sources & evidence

ORD record
ord-92c6bb1ee6f749d29567bed4593eedc0
Source dataset
uspto-grants-2011_04
Patent number
US07923559B2

Reaction notes

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