2-Cyanoacetyl chloride → HCID 178427865, compound

HRID 2404569Notes

Reaction equation

HRID 2404569 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([S:9][CH2:10][C:11]([F:14])([F:13])[F:12])=[CH:4][C:3]=1[NH:15][NH2:16].[C:17]([CH2:19][C:20](Cl)=[O:21])#[N:18]>O1CCCC1>[NH2:18][C:17]1[N:15]([C:3]2[CH:4]=[C:5]([S:9][CH2:10][C:11]([F:13])([F:14])[F:12])[C:6]([CH3:8])=[CH:7][C:2]=2[F:1])[N:16]=[C:20]([OH:21])[CH:19]=1

Participants

4

Reactant 2

HCID 110515942-Cyanoacetyl chlorideHCID 66842008HCID 66842008, compound

Product 1

HCID 178427865HCID 178427865, compoundYield 58.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

27.5 g of 2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phenylhydrazine was dissolved in 300 mL of tetrahydrofuran, and to this solution, 14 g of cyanoacetyl chloride was added, followed by stirring at room temperature for 5 minutes. Then, the solvent was distilled off under reduced pressure, the residue was dissolved in 300 mL of 1-propanol, and 10.6 g of methanesulfonic acid was added, followed by reflux with heating for 3 hours. After cooling to room temperature, the solvent was distilled off under reduced pressure, the reaction solution was neutralized to pH=7 with sodium hydrogen carbonate, and extraction with ethyl acetate was carried out. 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:acetic acid=50:50:1) to obtain 20.2 g of 5-amino-1-{2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phenyl}-3-hydroxypyrazole in the form of brown crystals (melting point: 110-113° C.).

Workup

  1. distillationThen, the solvent was distilled off under reduced pressure
  2. dissolutionthe residue was dissolved in 300 mL of 1-propanol
  3. addition10.6 g of methanesulfonic acid was added
  4. temperatureby reflux
  5. temperaturewith heating for 3 hours
  6. temperatureAfter cooling to room temperature
  7. distillationthe solvent was distilled off under reduced pressure
  8. extractionthe reaction solution was neutralized to pH=7 with sodium hydrogen carbonate, and extraction with ethyl acetate
  9. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  10. distillationthe solvent was distilled off under reduced pressure
  11. customthe obtained residue was purified by column chromatography (developing solvent ethyl acetate:hexane:acetic acid=50:50:1)

Sources & evidence

ORD record
ord-232863d59be8429eaefad2ace8501cb2
Source dataset
uspto-grants-2014_08
Patent number
US08802713B2

Reaction notes

Loading…