Sodium hydride → 2-Chloro-4-(5-fluoro-2-methyl-4-nitrophenoxy)pyridine

HRID 450432Notes

Reaction equation

HRID 450432 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][N:5]=1.F[C:12]1[CH:17]=[C:16]([F:18])[C:15]([N+:19]([O-:21])=[O:20])=[CH:14][C:13]=1[CH3:22]>CN(C=O)C>[Cl:3][C:4]1[CH:9]=[C:8]([O:10][C:12]2[CH:17]=[C:16]([F:18])[C:15]([N+:19]([O-:21])=[O:20])=[CH:14][C:13]=2[CH3:22])[CH:7]=[CH:6][N:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 186954591,5-Difluoro-2-methyl-4-nitrobenzeneHCID 178516507HCID 178516507, compound

Product 1

HCID 866416852-Chloro-4-(5-fluoro-2-methyl-4-nitrophenoxy)pyridineYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To 60% NaH in mineral oil (0.119 g, 2.97 mmol), under an atmosphere of argon, was added anhydrous DMF (3 mL) and the slurry was cooled in an ice bath. To this suspension was added, in portions, a solution of 2-chloropyridin-4-ol (0.35 g, 2.70 mmol) in DMF (2 mL). The reaction mixture was stirred cold for 5 minutes and then allowed to warm to RT and stirred for 20 minutes. 1,5-difluoro-2-methyl-4-nitrobenzene (0.514 g, 2.97 mmol) was added and the reaction mixture heated at 90° C. for 3 hours, cooled to RT, quenched with water and the mixture was extracted with EtOAc (3×). The combined organic phases were washed with brine, dried (Na2SO4), concentrated in vacuo and purified by silica gel column chromatography (EtOAc/hexanes) to obtain 2-chloro-4-(5-fluoro-2-methyl-4-nitrophenoxy)pyridine (0.48 g, 63% yield) MS (ESI) m/z: 283.0 (M+H+).

Workup

  1. temperaturethe slurry was cooled in an ice bath
  2. additionTo this suspension was added, in portions
  3. stirringstirred for 20 minutes
  4. temperaturethe reaction mixture heated at 90° C. for 3 hours
  5. temperaturecooled to RT
  6. customquenched with water
  7. extractionthe mixture was extracted with EtOAc (3×)
  8. washThe combined organic phases were washed with brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. custompurified by silica gel column chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-8e0f4bba7400497aa67b0fbd8f2656da
Source dataset
uspto-grants-2013_07
Patent number
US08486951B2

Reaction notes

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