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

HRID 2199249Notes

Reaction equation

HRID 2199249 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3](O)=[O:4].CN(C)C=O.P(Cl)(Cl)(Cl)=O.[NH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1.[O-]CC.[Na+].C(=O)([O-])[O-].[K+].[K+].[Cl:35][C:36]1[CH:41]=[CH:40][C:39]([CH2:42]Cl)=[CH:38][N:37]=1>CN1CCCC1=O.O>[Cl:35][C:36]1[N:37]=[CH:38][C:39]([CH2:42][N:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]2=[N:18][C:3](=[O:4])[C:2]([F:7])([F:6])[F:1])=[CH:40][CH:41]=1

Participants

10

Reactant 7

HCID 6228DimethylformamideHCID 6422Trifluoroacetic acidHCID 104392-AminopyridineHCID 11430Potassium CarbonateHCID 24813Phosphorus oxychlorideHCID 1554792-Chloro-5-(chloromethyl)pyridineHCID 2723922Sodium ethoxide

Product 1

HCID 14127920N-[1-[1-(6-Chloro-3-pyridyl)ethyl]-2-pyridylidene]-2,2,2-trifluoroacetamideYield 71.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
65 °C

Procedure

To 18.24 g (0.16 mol) of trifluoroacetic acid, 8.76 g (0.12 mol) of dimethylformamide was added. While the mixture was heated to 65° C., 12.26 g (0.08 mol) of phosphorus oxychloride was added to this mixture. Trifluoroacetyl chloride generated therefrom was bubbled into a solution which was obtained by dissolving 9.4 g (0.1 mol) of 2-aminopyridine in 80 mL of N-methylpyrrolidinone, and which was cooled to −15° C., and the mixture was stirred for 2 hours. While being cooled to −10° C., the reaction liquid was neutralized by adding 14.9 g (0.22 mol) of sodium ethoxide powder thereto. To this reaction liquid, 13.8 g (0.1 mol) of potassium carbonate powder and 16.2 g (0.1 mol) of 2-chloro-5-chloromethylpyridine were added, and distillation was conducted under reduced pressure (36 hPa) at 50 to 60° C. for 2 hours. To the reaction liquid, 20 mL of methanol was added, and the mixture was added to 400 ml of water heated to 50° C., while the vessel was also washed. After the mixture was stirred at room temperature for 30 minutes, the crystals were filtered, and washed with 100 mL of water and 50 mL of toluene. The obtained crystals were dried under reduced pressure at 45° C. Thus, 22.5 g of the target compound was obtained (Percentage Yield: 71.4%).

Workup

  1. customTrifluoroacetyl chloride generated therefrom was bubbled into a solution which
  2. customwas obtained
  3. temperaturewas cooled to −15° C.
  4. temperatureWhile being cooled to −10° C.
  5. customthe reaction liquid
  6. additionwere added
  7. distillationdistillation
  8. waitwas conducted under reduced pressure (36 hPa) at 50 to 60° C. for 2 hours
  9. customTo the reaction liquid, 20 mL of methanol
  10. additionwas added
  11. temperatureheated to 50° C., while the vessel
  12. washwas also washed
  13. stirringAfter the mixture was stirred at room temperature for 30 minutes
  14. filtrationthe crystals were filtered
  15. washwashed with 100 mL of water and 50 mL of toluene
  16. customThe obtained crystals were dried under reduced pressure at 45° C

Sources & evidence

ORD record
ord-01bb24c146844bcb9ea24f93f461d7b8
Source dataset
uspto-grants-2016_06
Patent number
US09357776B2

Reaction notes

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