Phenol → 2-Bromo-5-phenoxypyridine

HRID 432164Notes

Reaction equation

HRID 432164 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[Br:10][C:11]1[CH:16]=[C:15](Br)[CH:14]=[CH:13][N:12]=1>CN(C)C=O>[Br:10][C:11]1[CH:16]=[CH:15][C:14]([O:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:13][N:12]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 8171042,4-Dibromopyridine

Product 1

HCID 223469212-Bromo-5-phenoxypyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of phenol (1.99 g, 0.021 mol) in N,N-dimethylformamide (60 mL) was cooled to 0° C. and a 60% suspension of sodium hydride in parafine (0.89 g, 0.022 mol) was added at once. The mixture was stirred at this temperature for 10 min and 2,4-dibromopyridine was added at once. The mixture was allowed to warm up to ambient temperature while stirring under nitrogen for 72 hours and heated at 70° C. for 24 hours. The solvent was removed under reduced pressure; the residue was dissolved in ethyl acetate (150 mL) and washed with saturated aqueous sodium bicarbonate solution (100 mL), brine (80 mL), dried with magnesium sulfate and evaporated. The residue was purified by preparative RP-LC/MS (Gilson-Micromass C18, 5m, 130 A, 21 cm, 0%-100% acetonitrile-0.1M ammonium acetate over 9 min, 25 mL/min) to give 2-bromo-5-phenoxypyridine as a yellow oil (1.40 g, 0.0056 mol): 1H NMR (DMSO-d6, 400 MHz) 8.28 (s, 1H), 8.07 (d, 1H), 7.45 (t, 2H), 7.25 (t, 1H), 7.16 (d, 2H), 7.04 (d, 1H); MS: MH+250.

Workup

  1. stirringwhile stirring under nitrogen for 72 hours
  2. temperatureheated at 70° C. for 24 hours
  3. customThe solvent was removed under reduced pressure
  4. dissolutionthe residue was dissolved in ethyl acetate (150 mL)
  5. washwashed with saturated aqueous sodium bicarbonate solution (100 mL), brine (80 mL)
  6. dry with materialdried with magnesium sulfate
  7. customevaporated
  8. customThe residue was purified by preparative RP-LC/MS (Gilson-Micromass C18, 5m, 130 A, 21 cm, 0%-100% acetonitrile-0.1M ammonium acetate over 9 min, 25 mL/min)

Sources & evidence

ORD record
ord-f1fd33bd18b64eb4a5997ffa98b3a767
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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