Acetic Anhydride → HCID 86644469, compound

HRID 2404538Notes

Reaction equation

HRID 2404538 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[C:11]([S:13][CH2:14][C:15]([F:18])([F:17])[F:16])[C:10]([CH3:19])=[CH:9][C:8]=2[F:20])[N:5]=[C:4]([O:21][C:22]([F:30])([F:29])[CH:23]([F:28])[C:24]([F:27])([F:26])[F:25])[C:3]=1[Cl:31].[C:32](OC(=O)C)(=O)C>>[Cl:31][C:3]1[C:4]([O:21][C:22]([F:29])([F:30])[CH:23]([F:28])[C:24]([F:25])([F:26])[F:27])=[N:5][N:6]([C:7]2[CH:12]=[C:11]([S:13][CH2:14][C:15]([F:16])([F:18])[F:17])[C:10]([CH3:19])=[CH:9][C:8]=2[F:20])[C:2]=1[NH:1][CH3:32]

Participants

3

Reactant 2

HCID 7918Acetic AnhydrideHCID 86644467HCID 86644467, compound

Product 1

HCID 86644469HCID 86644469, compound

Procedure

0.8 g of 5-amino-4-chloro-1-{2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phenyl}-3-(1,1,2,3,3,3-hexafluoropropoxy)pyrazole was dissolved in 20 mL of acetic anhydride. After stirring for 3 hours under reflux with heating, acetic anhydride was distilled off under reduced pressure, the obtained residue was dissolved in 20 mL of tetrahydrofuran, and 20 mL of a 25 mass % ammonia water was added under cooling with ice. After stirring for one hour under cooling with ice, the solvent was distilled off under reduced pressure, extraction with ethyl acetate was carried out, and the organic layer was dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, the obtained residue was dissolved in 5 mL of dimethylformamide, and the solution was dropwise added to a suspension having 50 mg of sodium hydride suspended in 10 mL of dimethylformamide under cooling with ice. After completion of the dropwise addition, stirring was carried out at room temperature for 30 minutes. The reaction solution was cooled with ice again, and 0.18 g of methyl iodide was added, followed by stirring at room temperature for one hour. Water was injected, extraction with ethyl acetate was carried out, and after washing with water, the organic layer was dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, the obtained residue was dissolved in 10 mL of ethanol, and 10 mL of a 35 mass % hydrochloric acid aqueous solution was added, followed by stirring under reflux with heating for one hour. The reaction mixture was poured into water, extraction with ethyl acetate was carried out, and after washing with water, the organic layer was dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (developing solvent ethyl acetate:hexane=1:4) to obtain 0.34 g of 4-chloro-1-{2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phenyl}-3-(1,1,2,3,3,3-hexafluoropropoxy)-5-methylaminopyrazole.

Workup

  1. temperatureunder reflux
  2. temperaturewith heating
  3. distillationacetic anhydride was distilled off under reduced pressure
  4. dissolutionthe obtained residue was dissolved in 20 mL of tetrahydrofuran
  5. addition20 mL of a 25 mass % ammonia water was added
  6. temperatureunder cooling with ice
  7. stirringAfter stirring for one hour
  8. temperatureunder cooling with ice
  9. distillationthe solvent was distilled off under reduced pressure, extraction with ethyl acetate
  10. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  11. distillationThen, the solvent was distilled off under reduced pressure
  12. dissolutionthe obtained residue was dissolved in 5 mL of dimethylformamide
  13. additionthe solution was dropwise added to a suspension
  14. temperatureunder cooling with ice
  15. additionAfter completion of the dropwise addition
  16. stirringstirring
  17. waitwas carried out at room temperature for 30 minutes
  18. temperatureThe reaction solution was cooled with ice again
  19. addition0.18 g of methyl iodide was added
  20. stirringby stirring at room temperature for one hour
  21. extractionextraction with ethyl acetate
  22. washafter washing with water
  23. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  24. distillationThen, the solvent was distilled off under reduced pressure
  25. dissolutionthe obtained residue was dissolved in 10 mL of ethanol
  26. addition10 mL of a 35 mass % hydrochloric acid aqueous solution was added
  27. stirringby stirring
  28. temperatureunder reflux
  29. temperaturewith heating for one hour
  30. additionThe reaction mixture was poured into water, extraction with ethyl acetate
  31. washafter washing with water
  32. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  33. distillationThen, the solvent was distilled off under reduced pressure
  34. customthe obtained residue was purified by column chromatography (developing solvent ethyl acetate:hexane=1:4)

Sources & evidence

ORD record
ord-81fd3f70e5f946fcb04118e20d94f55c
Source dataset
uspto-grants-2014_08
Patent number
US08802713B2

Reaction notes

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