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

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Reaction Steps

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%).

Provenance & Evidence