Sodium hydride → 1-methyl-5-(2-nitro-phenylamino)-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 220793Notes

Reaction equation

HRID 220793 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1[CH:9]=[N:10][N:11]([CH3:14])[C:12]=1[NH2:13])=[O:7])[CH3:4].F[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[N+:22]([O-:24])=[O:23].OS([O-])(=O)=O.[K+]>C1COCC1.CCOC(C)=O>[CH2:3]([O:5][C:6]([C:8]1[CH:9]=[N:10][N:11]([CH3:14])[C:12]=1[NH:13][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[N+:22]([O-:24])=[O:23])=[O:7])[CH3:4]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 738951-Fluoro-2-nitrobenzeneHCID 271299Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylateHCID 516920Potassium bisulfate

Product 1

HCID 145905801-methyl-5-(2-nitro-phenylamino)-1H-pyrazole-4-carboxylic acid ethyl esterYield 58%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (60% dispersion in oil, 7.0 g, 170 mmol) was added portionwise to a suspension of 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (21.1 g, 125 mmol) in anhydrous THF (300 ml) at 0° C. The mixture was allowed to warm to room temperature and stirred for 0.75 h then cooled to 0° C. 1-fluoro-2-nitrobenzene (17.6 g, 125 mmol) was added and the resultant suspension was stirred at room temperature for 18 h. EtOAc and 0.3M KHSO4 were added and separated. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant 50% hexanes/50% ethyl acetate) to yield the title compound (20.8 g, 58%).

Workup

  1. temperaturethen cooled to 0° C
  2. customseparated
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washthe combined organic layers were washed with brine
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel (eluant 50% hexanes/50% ethyl acetate)

Sources & evidence

ORD record
ord-4ed2c5fde73146548312970ab47e7d28
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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