Sodium hydride → 1-(2-Benzoyl-4-nitrophenyl)-3,5-pyrazole dicarboxylic acid dimethyl ester

Participants

Reaction Steps

To a slurry of 5.3 g. (110 mmol) of 50% NaH in mineral oil in 425 ml. of dry DMF, stirred at 3° under argon, was added portionwise over a 20 minute time period, 20.26 g. (110 mmol) of 3,5-pyrazole dicarboxylic acid dimethyl ester*, maintaining a temperature of 5°-8°. When the vigorous hydrogen evolution had stopped, the ice bath was removed and the reaction allowed to warm to room temperature while stirring for 20 minutes. A solution of 24.5 g. (100 mmol) of 2-fluoro-5-nitrobenzophenone, in 100 ml. of dry DMF was added dropwise over 40 minutes and when addition was complete, the reaction was heated at 65° for 1.5 hr. After cooling, the mixture was poured over a mixture of ice and brine and extracted well with a 1:1 EtOAc:ether mixture. The combined extracts were washed with brine, dried over MgSO4 and concentrated. The crude mixture was chromatographed on silica gel using as an eluent benzene mixed with 0-100% EtOAc. The residue remaining after the solvents were evaporated was recrystallized from EtOAc/hexane to give the final product. The analytical sample was prepared by an additional recrystallization from EtOAc/hexane and was obtained as off-white needles: mp 150°-152°.

Provenance & Evidence