Trifluoroacetic acid → N-[1-[1-(6-Chloro-3-pyridyl)ethyl]-2-pyridylidene]-2,2,2-trifluoroacetamide

HRID 2199242Notes

Reaction equation

HRID 2199242 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[F:8][C:9]([F:14])([F:13])[C:10](O)=[O:11].P(Cl)(Cl)(Cl)=O.C(=O)([O-])[O-].[K+].[K+].[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33]Cl)=[CH:29][N:28]=1>C1(C)C=CC=CC=1.O.CN(C)C=O>[Cl:26][C:27]1[N:28]=[CH:29][C:30]([CH2:33][N:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]2=[N:1][C:10](=[O:11])[C:9]([F:14])([F:13])[F:8])=[CH:31][CH:32]=1

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 104392-AminopyridineHCID 11430Potassium Carbonate2×HCID 24813Phosphorus oxychlorideHCID 1554792-Chloro-5-(chloromethyl)pyridine

Product 1

HCID 14127920N-[1-[1-(6-Chloro-3-pyridyl)ethyl]-2-pyridylidene]-2,2,2-trifluoroacetamideYield 77%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
5 °C

Procedure

In 100 ml of toluene, 10.0 g (0.106 mol) of 2-aminopyridine was dissolved. After the solution was cooled to 5° C., 11.8 ml (0.159 mol) of trifluoroacetic acid and 9.9 ml (0.106 mol) of phosphorus oxychloride were added, followed by stirring at room temperature overnight. Then, 20 ml of toluene was distilled off under reduced pressure. To the reaction liquid, 50 ml of dimethylformamide, 35.28 g (0.256 mol) of potassium carbonate powder, and 17.22 g (0.106 mol) of 2-chloro-5-chloromethylpyridine were added under ice-cooling. Then, distillation was conducted under reduced pressure (60 to 35 hPa) at 50 to 60° C. Two hours later, 25 ml of dimethylformamide, 20 ml of toluene, and 7.35 g (0.053 mol) of potassium carbonate powder were further added, and then distillation was conducted under reduced pressure (60 to 35 hPa) at 50 to 60° C. for 2 hours. To the reaction liquid, 60 ml of methanol and 50 ml of water were added, and the reaction liquid was added to 300 ml of water, while the vessel was also washed. Thirty minutes later, the crystals were filtered, and washed with 70 ml of water and 40 ml of toluene. The obtained crystals were dried under reduced pressure at 60° C. Thus, 25.75 g of the target compound was obtained (76.9%).

Workup

  1. distillationThen, 20 ml of toluene was distilled off under reduced pressure
  2. additionwere added under ice-
  3. temperaturecooling
  4. distillationThen, distillation
  5. customwas conducted under reduced pressure (60 to 35 hPa) at 50 to 60° C
  6. distillationdistillation
  7. waitwas conducted under reduced pressure (60 to 35 hPa) at 50 to 60° C. for 2 hours
  8. customTo the reaction liquid, 60 ml of methanol and 50 ml of water
  9. additionwere added
  10. customthe reaction liquid
  11. washwas also washed
  12. filtrationThirty minutes later, the crystals were filtered
  13. washwashed with 70 ml of water and 40 ml of toluene
  14. customThe obtained crystals were dried under reduced pressure at 60° C

Sources & evidence

ORD record
ord-8fc531bddb7c4f99a617e754711d580f
Source dataset
uspto-grants-2016_06
Patent number
US09357776B2

Reaction notes

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