Sodium hydride → 4-(4-Bromo-3-fluorophenoxy)-2-methylpyridine 1-oxide

HRID 1627018Notes

Reaction equation

HRID 1627018 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].[H-].[Na+].[N+]([C:15]1[CH:16]=[C:17]([CH3:22])[N+:18]([O-:21])=[CH:19][CH:20]=1)([O-])=O>CN(C=O)C.CCOC(C)=O.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:15]2[CH:20]=[CH:19][N+:18]([O-:21])=[C:17]([CH3:22])[CH:16]=2)=[CH:4][C:3]=1[F:9]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 95291Pyridine, 2-methyl-4-nitro-, 1-oxideHCID 27791534-Bromo-3-fluorophenol

Product 1

HCID 592873124-(4-Bromo-3-fluorophenoxy)-2-methylpyridine 1-oxide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
180 °C

Procedure

To a mixture of 4-bromo-3-fluorophenol (6 g, 31.41 mmol) in DMF (20 ml) was added NaH (0.81 g, 56 mmol, 60% in mineral oil) at room temperature. The resulting reaction mixture was stirred for 10 min., then, 4-nitro-2-picoline N-oxide (5.6 g, 36.12 mmol) was added. The resulting solution was subjected to microwave heating at 180° C. for 1 h. The mixture was cooled to room temperature and diluted with EtOAc and H2O. Layers were separated and the aqueous layer was extracted twice with EtOAc. The combined organic extracts were dried (Na2SO4) and evaporated in vacuo. The residue thus obtained was purified by column chromatography (silica gel; DCM/MeOH(NH3) up to 2% as eluent). The desired fractions were collected and evaporated in vacuo to yield compound D14 (3.61 g, 39%) as dark orange solid.

Workup

  1. customThe resulting reaction mixture
  2. temperatureThe mixture was cooled to room temperature
  3. customLayers were separated
  4. extractionthe aqueous layer was extracted twice with EtOAc
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. customevaporated in vacuo
  7. customThe residue thus obtained
  8. customwas purified by column chromatography (silica gel; DCM/MeOH(NH3) up to 2% as eluent)
  9. customThe desired fractions were collected
  10. customevaporated in vacuo
  11. customto yield compound D14 (3.61 g, 39%) as dark orange solid

Sources & evidence

ORD record
ord-c4ee302caeb04e70ae11bdec0b6cd90c
Source dataset
uspto-grants-2014_07
Patent number
US08785486B2

Reaction notes

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