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

HRID 2199256Notes

Reaction equation

HRID 2199256 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[F:8][C:9]([F:16])([F:15])[C:10]([O:12]CC)=O.FC(F)(F)C(OC(=O)C(F)(F)F)=O.[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([CH2:37]Cl)=[CH:33][N:32]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C1(C)C=CC=CC=1>[Cl:30][C:31]1[N:32]=[CH:33][C:34]([CH2:37][N:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]2=[N:1][C:10](=[O:12])[C:9]([F:8])([F:15])[F:16])=[CH:35][CH:36]=1

Participants

8

Reactant 5

HCID 9794Ethyl trifluoroacetateHCID 9845Trifluoroacetic anhydrideHCID 104392-AminopyridineHCID 11430Potassium CarbonateHCID 1554792-Chloro-5-(chloromethyl)pyridine

Product 1

HCID 14127920N-[1-[1-(6-Chloro-3-pyridyl)ethyl]-2-pyridylidene]-2,2,2-trifluoroacetamideYield 72%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
62.5 °C

Procedure

In 30 mL of dimethylformamide and 20 mL of toluene, 9.4 g (0.1 mol) of 2-aminopyridine was dissolved. To the solution, 21.3 g (0.15 mol) of ethyl trifluoroacetate was added, followed by stirring at 60 to 65° C. for 7.5 hours. After concentration under reduced pressure (90 hPa, 40° C.), the residue was cooled on ice, and 20 mL of toluene and 10.5 g (0.05 mol) of trifluoroacetic anhydride were added to the residue, followed by stirring at room temperature for 1 hour. Subsequently, 16.2 g (0.1 mol) of 2-chloro-5-chloromethylpyridine, 20 mL of dimethylformamide, and 16.6 g (0.12 mol) of potassium carbonate were added, followed by stirring under a reduced pressure of 110 hPa at 60 to 65° C. for 4 hours. After concentration under reduced pressure (90 hPa, 50° C.), 25 mL of methanol was added to the reaction liquid, and the mixture was added to 250 mL of hot water of 50° C. Then, the mixture was cooled to room temperature with stirring. Crystals were filtered, and washed with 90 mL of water and 90 mL of toluene. The obtained crystals were dried under reduced pressure at 60° C. Thus, 22.68 g of the target compound was obtained (Percentage Yield: 72.0%).

Workup

  1. concentrationAfter concentration under reduced pressure (90 hPa, 40° C.)
  2. additionwere added to the residue
  3. stirringby stirring at room temperature for 1 hour
  4. stirringby stirring under a reduced pressure of 110 hPa at 60 to 65° C. for 4 hours
  5. concentrationAfter concentration under reduced pressure (90 hPa, 50° C.), 25 mL of methanol
  6. additionwas added to the reaction liquid
  7. additionthe mixture was added to 250 mL of hot water of 50° C
  8. temperatureThen, the mixture was cooled to room temperature
  9. stirringwith stirring
  10. filtrationCrystals were filtered
  11. washwashed with 90 mL of water and 90 mL of toluene
  12. customThe obtained crystals were dried under reduced pressure at 60° C

Sources & evidence

ORD record
ord-7c744bd094e2479292987210aaae268e
Source dataset
uspto-grants-2016_06
Patent number
US09357776B2

Reaction notes

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