Tetrahydrofuran → 1-Methyl-5-(4-methyl-2-nitro-phenylamino)-1H-pyrazole-4-carboxylic Acid Ethyl Ester
Reaction equation
[H-].[Na+].[NH2:3][C:4]1[N:8]([CH3:9])[N:7]=[CH:6][C:5]=1[C:10]([O:12][CH2:13][CH3:14])=[O:11].F[C:16]1[CH:17]=[C:18](C)[CH:19]=[CH:20][C:21]=1[N+:22]([O-:24])=[O:23].[CH2:26]1COCC1>>[CH2:13]([O:12][C:10]([C:5]1[CH:6]=[N:7][N:8]([CH3:9])[C:4]=1[NH:3][C:20]1[CH:19]=[CH:18][C:17]([CH3:26])=[CH:16][C:21]=1[N+:22]([O-:24])=[O:23])=[O:11])[CH3:14]Participants
Procedure
Sodium hydride (60% dispersion in oil, 7.28 g, 180 mmol) was added portionwise to a solution of ethyl 5-amino-1-methylpyrazole-4-carboxylate (21.8 g, 148 mmol) in anhydrous THF at 0° C. The mixture was allowed to warm to room temperature and stirred for 1 h then a solution of 3-fluoro-4-nitrotoluene (20 g, 129 mmol) in anhydrous THF (50 ml) was added dropwise. The resultant deep purple solution was stirred at room temperature for 18 h then poured into ice-cold 1N hydrochloric acid. The resulting mixture was extracted with dichloromethane (200 ml×2), and the combined organic extracts were washed with brine and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 60% pet ether:40% EtOAc) to yield the title compound (28.00 g, 61%).
Workup
- stirringThe resultant deep purple solution was stirred at room temperature for 18 h
- extractionThe resulting mixture was extracted with dichloromethane (200 ml×2)
- washthe combined organic extracts were washed with brine
- concentrationconcentrated in vacuo
- customThe residue was purified by flash chromatography on silica gel (eluant; 60% pet ether:40% EtOAc)
Sources & evidence
- ORD record
- ord-0c6ae671ac61425195c3e70b36e940cd
- Source dataset
- uspto-grants-2012_06
- Patent number
- US08202858B2
Reaction notes
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