Diethyl Ether → Diisopropyl Ether
Reaction equation
[F:1][C:2]([F:16])([F:15])[CH2:3][S:4][C:5]1[C:6]([CH3:14])=[CH:7][C:8]([F:13])=[C:9]([NH:11][NH2:12])[CH:10]=1.[C:17](O[C:21](=[O:23])[CH3:22])(=[O:19])[CH3:18].[CH2:24](OCC)C>>[CH:21]([O:23][CH:9]([CH3:8])[CH3:10])([CH3:24])[CH3:22].[F:13][C:8]1[CH:7]=[C:6]([CH3:14])[C:5]([S:4][CH2:3][C:2]([F:1])([F:15])[F:16])=[CH:10][C:9]=1[NH:11][NH:12][C:17](=[O:19])[CH3:18]Participants
Procedure
4.6 g of 1-(5-(2,2,2-trifluoroethylthio)-2-fluoro-4-methylphenyl)hydrazine was dissolved in 100 mL of diethyl ether, and 1.85 g of acetic anhydride was dropwise added under cooling with ice, followed by stirring at room temperature for one hour. The obtained crystals were collected by filtration and washed with a solution of hexane:diisopropyl ether=3:1 (mass ratio) to obtain 4.41 g of N′-{2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phenyl}acetohydrazide in the form of colorless crystals. Then, to 4.4 g of this hydrazide, 1.93 g of ethyl acetoacetate and 4.02 g of phosphorus tribromide were added, followed by stirring at 50° C. for 2 hours. Then, after stirring under cooling with ice for 10 minutes, ice was put, and the pH was adjusted to 5 with a 1N sodium hydroxide aqueous solution. Then, extraction with ethyl acetate was carried out, followed by washing with a saturated salt solution, the organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (ethyl acetate:hexane=1:3) to obtain 2.03 g of 1-{2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phenyl}-3-hydroxy-5-methylpyrazole in the form of colorless solid.
Workup
- temperatureunder cooling with ice
- filtrationThe obtained crystals were collected by filtration
- washwashed with a solution of hexane
Sources & evidence
- ORD record
- ord-8913ca882d964fe8a7ceec9a6ae3f260
- Source dataset
- uspto-grants-2014_08
- Patent number
- US08802713B2
Reaction notes
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