Hydrochloric Acid → Ethyl 1-(5-chloro-3-fluoropyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylate
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([F:10])[C:5]([NH:8][NH2:9])=[N:6][CH:7]=1.CCOC=[CH:15][C:16](=O)[CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19].Cl.[CH2:25](O)C>>[CH2:21]([O:20][C:18]([C:17]1[CH:25]=[N:9][N:8]([C:5]2[C:4]([F:10])=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=2)[C:16]=1[CH3:15])=[O:19])[CH3:22]Participants
Procedure
5-Chloro-3-fluoro-2-hydrazinylpyridine (5 g) and ethyl (2-ethoxymethylene)-acetoacetate (5.76 g) synthesized according to the method described in J. Chem. Soc. Perkin trans. I, p. 1875 (1988) were added to a mixed solvent of 1 N hydrochloric acid aqueous solution (150 ml) and ethanol (100 ml), and stirred under reflux. After completion of the reaction, the mixture was allowed to cool, and the organic solvent was evaporated in vacuo. Then, the mixture was extracted with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, and then the solvent was evaporated in vacuo. The obtained residue was purified with silica gel column chromatography (n-hexane/ethyl acetate) to give 1-(5-chloro-3-fluoropyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (6.95 g) as a pale yellow solid. MS (ESI) m/z: 284 (M+H)+.
Workup
- temperatureunder reflux
- customAfter completion of the reaction
- temperatureto cool
- customthe organic solvent was evaporated in vacuo
- extractionThen, the mixture was extracted with ethyl acetate
- dry with materialthe organic layer was dried over anhydrous sodium sulfate
- customthe solvent was evaporated in vacuo
- customThe obtained residue was purified with silica gel column chromatography (n-hexane/ethyl acetate)
Sources & evidence
- ORD record
- ord-bb03c8d515fb4d0bb27c1864b14518fe
- Source dataset
- uspto-grants-2015_10
- Patent number
- US09150555B2
Reaction notes
Loading…