Ammonia → HCID 54141266, compound

Participants

Reaction Steps

A solution of 14.0 g (0.202 mol) of sodium nitrite in 80 ml of water is added dropwise, at 0° C., to a suspension of 25.5 g (0.2 mol) of 3-chloroaniline in 80 ml of water and 65 ml of concentrated hydrochloric acid. After stirring for 15 minutes to complete the reaction, the foamy brown solution is poured into a mixture of 33.1 g (0.201 mol) of 2-chloroacetoacetic acid ethyl ester, 90 g of sodium acetate in 160 ml of water and 200 ml of ethanol. The whole is then stirred at 10° C. for 3 hours to complete the reaction. After the addition of 1 liter of water, a red oil separates and is extracted with ethyl acetate. After drying with magnesium sulfate and concentrating the extract there is obtained, in quantitative yield, an orange-red, crystalline material which is dissolved in 320 ml of tetrahydrofuran. 35 g (0.625 mol) of 25% aqueous ammonia are added dropwise at 15°-20° C. and the whole is then stirred for two hours. The end of the reaction is determined by thin-layer chromatography. 1 liter of water is then added and the resulting oil is extracted with ethyl acetate. After drying and concentrating the extract by evaporation, 40.7 g (84.4% of the theoretical yield) of an intermediate are obtained. 4.8 g (0.02 mol) thereof are dissolved in 30 ml of toluene, and 2.5 ml (0.021 mol) of 2-fluorobenzoyl chloride are added thereto. The clear, brown reaction solution is heated until water and hydrochloric acid separate out and the solvent has been distilled off. The residue is subjected to preliminary purification over a short column of silica gel and is then recrystallised from ether/hexane to yield 3.6 g (52.2% of the theoretical yield) of 1-(3-chlorophenyl)-5-(2-fluorophenyl)-1,2,4-triazole-3-carboxylic acid ethyl ester in the form of white-beige crystals melting at 77°-78° C.

Provenance & Evidence