Sodium hydride → HCID 59287310, compound

HRID 2176850Notes

Reaction equation

HRID 2176850 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[CH:3]=1.[H-].[Na+].[CH3:12][C:13]1[C:18]([CH3:19])=[C:17]([N+]([O-])=O)[CH:16]=[CH:15][N+:14]=1[O-:23]>CN1CCCC1=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:17]2[CH:16]=[CH:15][N+:14]([O-:23])=[C:13]([CH3:12])[C:18]=2[CH3:19])=[C:4]([F:9])[CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1482232,3-Dimethyl-4-nitropyridine-N-oxideHCID 27249814-Bromo-2-fluorophenol

Product 1

HCID 59287310HCID 59287310, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
180 °C

Procedure

To a room temperature solution of 4-bromo-2-fluorophenol (1 g, 5.23 mmol) in N-methylpyrrolidone (10 ml) was added sodium hydride (0.27 g, 6.79 mmol, 60% in mineral oil) portionwise. After stirring for 10 minutes 2,3-dimethyl-4-nitro-pyridine 1-oxide (1.05 g, 6.28 mmol) was added The reaction mixture was heated at 180° C. for 60 minutes under microwave irradiation. After cooling to room temperature the mixture was filtered through a diatomaceous earth pad and the filtrate was then diluted with EtOAc and washed with water. The solution was then extracted with additional EtOAc (2×150 ml). The organic layer was dried (Na2SO4) and the solvent evaporated in vacuo. The crude product was purified by column chromatography (silica gel; DCM to DCM/MeOH up to 3% as eluent). The desired fractions were collected and evaporated in vacuo to yield intermediate 23 (0.75 g, 46%).

Workup

  1. additionwas added The reaction mixture
  2. temperatureAfter cooling to room temperature the mixture
  3. filtrationwas filtered through a diatomaceous earth pad
  4. additionthe filtrate was then diluted with EtOAc
  5. washwashed with water
  6. extractionThe solution was then extracted with additional EtOAc (2×150 ml)
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. customthe solvent evaporated in vacuo
  9. customThe crude product was purified by column chromatography (silica gel
  10. customThe desired fractions were collected
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-7505194fa5444e23a8d592c1595734af
Source dataset
uspto-grants-2015_06
Patent number
US09067891B2

Reaction notes

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