Azobisisobutyronitrile → [6-(2,5-Difluorobenzoyl)pyridin-3-yl]methyl acetate

HRID 748832Notes

Reaction equation

HRID 748832 reaction equation
BrN1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N.[F:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=1[CH:29]([OH:37])[C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][N:31]=1.S([O-])([O-])(=O)=S.[Na+].[Na+].[C:45]([O-:48])(=[O:47])[CH3:46].[Na+]>C(Cl)(Cl)(Cl)Cl.C(OCC)(=O)C>[C:45]([O:48][CH2:36][C:33]1[CH:32]=[N:31][C:30]([C:29]([C:23]2[CH:24]=[C:25]([F:28])[CH:26]=[CH:27][C:22]=2[F:21])=[O:37])=[CH:35][CH:34]=1)(=[O:47])[CH3:46]

Participants

8

Reactant 5

HCID 6547AzobisisobutyronitrileHCID 24477Sodium ThiosulfateHCID 67184N-bromobutanimideHCID 517045Sodium AcetateHCID 23114839HCID 23114839, compound

Product 1

HCID 23114640[6-(2,5-Difluorobenzoyl)pyridin-3-yl]methyl acetateYield 18.4%

Reagents, catalysts & solvents 2

HCID 5943Carbon TetrachlorideSolventHCID 8857Ethyl AcetateSolvent

Procedure

While heating under reflux, N-bromosuccinimide (6.0 g, 33.6 mmol) and a catalytic amount of 2,2′-azobis(2-methylpropionitrile) were added to a solution of the 2-[(2,5-difluorophenyl)-hydroxymethyl]-5-methylpyridine (2.64 g, 11.2 mmol), which had been obtained in Referential Example 15, in carbon tetrachloride (60 ml). The resulting mixture was then, stirred. After reflux for 7 hours, the reaction mixture was cooled to room temperature and added to an aqueous solution of sodium thiosulfate. The mixture was extracted with ether. The solution was washed with water and brine, and then dried over sodium sulfate. The residue obtained by concentrating the solution under reduced pressure was dissolved in toluene and the resulting solution was concentrated again. The residue was dissolved in N,N-dimethylformamide (20 ml). Sodium acetate (4.59 g, 56 mmol) was added to the resulting solution and the mixture was stirred at 70° C. for 17 hours. After cooling, the reaction mixture was dissolved in ethyl acetate (100 ml), followed by washing with water and brine. The solution was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate=5:1) to yield the title compound (600 mg, 18%) as an oil.

Workup

  1. temperatureWhile heating
  2. temperatureunder reflux
  3. temperatureAfter reflux for 7 hours
  4. extractionThe mixture was extracted with ether
  5. washThe solution was washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. customThe residue obtained
  8. concentrationby concentrating the solution under reduced pressure
  9. dissolutionwas dissolved in toluene
  10. concentrationthe resulting solution was concentrated again
  11. dissolutionThe residue was dissolved in N,N-dimethylformamide (20 ml)
  12. stirringthe mixture was stirred at 70° C. for 17 hours
  13. temperatureAfter cooling
  14. washby washing with water and brine
  15. dry with materialThe solution was dried over anhydrous magnesium sulfate
  16. concentrationconcentrated under reduced pressure
  17. customThe residue was purified by silica gel chromatography (hexane:ethyl acetate=5:1)

Sources & evidence

ORD record
ord-268c71bd663344c8b582f74ff5d83235
Source dataset
uspto-grants-2008_07
Patent number
US07399775B2

Reaction notes

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