Water → HCID 86644450, compound

HRID 2404522Notes

Reaction equation

HRID 2404522 reaction equation
[C:1]([NH:4][C:5]1[N:9]([C:10]2[CH:15]=[C:14]([S:16][CH2:17][C:18]([F:21])([F:20])[F:19])[C:13]([CH3:22])=[CH:12][C:11]=2[F:23])[N:8]=[C:7]([O:24][CH2:25][C:26]([F:32])([F:31])[C:27]([F:30])([F:29])[F:28])[CH:6]=1)(=O)[CH3:2].[H-].[Na+].Br[CH2:36]C#C.O>CN(C)C=O.C(OCC)(=O)C>[F:23][C:11]1[CH:12]=[C:13]([CH3:22])[C:14]([S:16][CH2:17][C:18]([F:19])([F:20])[F:21])=[CH:15][C:10]=1[N:9]1[C:5]([NH:4][CH2:1][C:2]#[CH:36])=[CH:6][C:7]([O:24][CH2:25][C:26]([F:32])([F:31])[C:27]([F:29])([F:30])[F:28])=[N:8]1

Participants

7

Reactant 4

HCID 962WaterHCID 7842Propargyl bromideHCID 24758Sodium hydrideHCID 86644422HCID 86644422, compound

Product 1

HCID 86644450HCID 86644450, compoundYield 70.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2.0 g of 5-acetylamino-1-{2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phenyl}-3-(2,2,3,3,3-pentafluoropropoxy)pyrazole was dissolved in 15 mL of dimethylformamide, and under cooling with ice, the solution was dropwise added to a suspension having 0.23 g of sodium hydride suspended in 10 mL of dimethylformamide, and after completion of the dropwise addition, stirring was carried out at room temperature for 30minutes. The reaction solution was cooled with ice again, and 0.72 g of 1-bromo-2-propyne was added, followed by stirring at room temperature for 1 hour. Then, 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. The solvent was distilled off under reduced pressure, the obtained residue was dissolved in 20 mL of ethanol, and 20 mL of a 35 mass % hydrochloric acid aqueous solution was added, followed by stirring under reflux with heating for 2 hours. 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. 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 1.4 g of 1-{2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phenyl}-3-(2,2,3,3,3-pentafluoropropoxy)-5-(2-propynylamino)pyrazole.

Workup

  1. temperatureunder cooling with ice
  2. additionthe solution was dropwise added to a suspension
  3. additionafter completion of the dropwise addition
  4. temperatureThe reaction solution was cooled with ice again
  5. stirringby stirring at room temperature for 1 hour
  6. washafter washing with water
  7. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  8. distillationThe solvent was distilled off under reduced pressure
  9. dissolutionthe obtained residue was dissolved in 20 mL of ethanol
  10. addition20 mL of a 35 mass % hydrochloric acid aqueous solution was added
  11. stirringby stirring
  12. temperatureunder reflux
  13. temperaturewith heating for 2 hours
  14. additionThe reaction mixture was poured into water, extraction with ethyl acetate
  15. washafter washing with water
  16. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  17. distillationThe solvent was distilled off under reduced pressure
  18. customthe obtained residue was purified by column chromatography (developing solvent ethyl acetate:hexane=1:4)

Sources & evidence

ORD record
ord-ed65fd61c08b4ad6b57ffeedfd14ad64
Source dataset
uspto-grants-2014_08
Patent number
US08802713B2

Reaction notes

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