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

HRID 2199248Notes

Reaction equation

HRID 2199248 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3](O)=[O:4].S(Cl)(Cl)=O.[NH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32]Cl)=[CH:28][N:27]=1>CN1CCCC1=O.O.C1(C)C=CC=CC=1.CN(C)C=O>[Cl:25][C:26]1[N:27]=[CH:28][C:29]([CH2:32][N:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]2=[N:12][C:3](=[O:4])[C:2]([F:7])([F:6])[F:1])=[CH:30][CH:31]=1

Participants

10

Reactant 5

HCID 6422Trifluoroacetic acidHCID 104392-AminopyridineHCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 1554792-Chloro-5-(chloromethyl)pyridine

Product 1

HCID 14127920N-[1-[1-(6-Chloro-3-pyridyl)ethyl]-2-pyridylidene]-2,2,2-trifluoroacetamideYield 53.3%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
65 °C

Procedure

To 13.68 g (0.12 mol) of trifluoroacetic acid, 1.5 mL of dimethylformamide was added. Then, 14.28 g (0.12 mol) of thionyl chloride was added to the mixture, which was heated to 65° C. Trifluoroacetyl chloride generated therefrom was bubbled into a solution which was obtained by dissolving 9.4 g (0.1 mol) of 2-aminopyridine in 50 mL of N-methylpyrrolidone, and which was cooled to −10° C., and the mixture was stirred for 1 hour. To the reaction liquid, 100 mL of toluene, 48.3 g (0.35 mol) of potassium carbonate powder, and 16.52 g (0.102 mol) of 2-chloro-5-chloromethylpyridine were added, and distillation was conducted under reduced pressure (36 hPa) at 50 to 60° C. for 3 hours. To the reaction liquid, 20 mL of methanol was added, and the mixture was added to 300 ml of water heated to 50° C., while the vessel was also washed. The mixture was stirred at room temperature for 1.5 hours. Then, the crystals were filtered, and washed with 100 mL of water and 150 mL of toluene. The obtained crystals were dried under reduced pressure at 45° C. Thus, 16.8 g of the target compound was obtained (Percentage Yield: 53.3%).

Workup

  1. customTrifluoroacetyl chloride generated therefrom was bubbled into a solution which
  2. customwas obtained
  3. temperaturewas cooled to −10° C.
  4. additionwere added
  5. distillationdistillation
  6. waitwas conducted under reduced pressure (36 hPa) at 50 to 60° C. for 3 hours
  7. customTo the reaction liquid, 20 mL of methanol
  8. additionwas added
  9. temperatureheated to 50° C., while the vessel
  10. washwas also washed
  11. stirringThe mixture was stirred at room temperature for 1.5 hours
  12. filtrationThen, the crystals were filtered
  13. washwashed with 100 mL of water and 150 mL of toluene
  14. customThe obtained crystals were dried under reduced pressure at 45° C

Sources & evidence

ORD record
ord-217b3c87b82f4befaf7838eed0115155
Source dataset
uspto-grants-2016_06
Patent number
US09357776B2

Reaction notes

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