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

HRID 889637Notes

Reaction equation

HRID 889637 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>[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

5

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 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
180 °C

Procedure

4-Bromo-3-fluorophenol (0.5 g, 2.61 mmol) was added to a solution of sodium hydride (0.115 g, 2.90 mmol) in DMF (5 ml). After stirring for 10 minutes 4-nitro-2-picoline N-oxide (0.37 g, 2.41 mmol) was added. The reaction mixture was heated at 180° C. for 1 hour under microwave irradiation. After cooling to room temperature the mixture was filtered through diatomaceous earth and this was thoroughly washed with EtOAc. The filtrate was washed with water (2×25 ml), the organic fraction was dried (Na2SO4) and the solvent evaporated in vacuo. The crude product was purified by column chromatography (silica gel; 0-3% methanol/DCM as eluent). The desired fractions were collected and evaporated in vacuo to yield intermediate D12 (0.33 g, 49%).

Workup

  1. additionwas added
  2. temperatureAfter cooling to room temperature the mixture
  3. filtrationwas filtered through diatomaceous earth
  4. washthis was thoroughly washed with EtOAc
  5. washThe filtrate was washed with water (2×25 ml)
  6. dry with materialthe organic fraction was dried (Na2SO4)
  7. customthe solvent evaporated in vacuo
  8. customThe crude product was purified by column chromatography (silica gel; 0-3% methanol/DCM as eluent)
  9. customThe desired fractions were collected
  10. customevaporated in vacuo
  11. customto yield intermediate D12 (0.33 g, 49%)

Sources & evidence

ORD record
ord-6b27dcb62bea4fe7b62f0c694ab9f1cf
Source dataset
uspto-grants-2012_08
Patent number
US08252937B2

Reaction notes

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