Acetic Anhydride → HCID 86644469, compound

Participants

Reaction Steps

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.

Provenance & Evidence