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

HRID 2199244Notes

Reaction equation

HRID 2199244 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 70.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 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., 11.84 ml (0.159 mol) of trifluoroacetic acid and subsequently 5.94 ml (0.064 mol) of phosphorus oxychloride were added thereto, 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, 22.03 g (0.16 mol) of potassium carbonate powder, and 17.56 g (0.108 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. One hour later, 20 ml of dimethylformamide, 20 ml of toluene, and 4.41 g (0.032 mol) of potassium carbonate powder were further added thereto, and distillation was conducted under reduced pressure (60 to 35 hPa) and 50 to 60° C. for 1.5 hours. The reaction liquid to which 30 ml of methanol was added was added to 250 ml of water of 50° C. Then, 50 ml of water was added thereto, while the vessel was also washed therewith. After being cooled to room temperature, the mixture was stirred for 30 minutes. The crystals were filtered, and washed with 50 ml of water and 30 ml of toluene. The obtained crystals were dried under reduced pressure at 60° C. Thus, 23.69 g of the target compound was obtained (70.6%).

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) and 50 to 60° C. for 1.5 hours
  8. customThe reaction liquid to which 30 ml of methanol
  9. additionwas added
  10. washwhile the vessel was also washed
  11. temperatureAfter being cooled to room temperature
  12. stirringthe mixture was stirred for 30 minutes
  13. filtrationThe crystals were filtered
  14. washwashed with 50 ml of water and 30 ml of toluene
  15. customThe obtained crystals were dried under reduced pressure at 60° C

Sources & evidence

ORD record
ord-15be469d3b4a4f98acb1c2ad70469b8c
Source dataset
uspto-grants-2016_06
Patent number
US09357776B2

Reaction notes

Loading…