4-Bromoaniline → N-(4-bromophenyl)-1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

Participants

Reaction Steps

In a 500 mL round bottom flask crude 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carbonyl chloride (47 mmol) was dissolved in 200 mL CH2Cl2 to afford a dark solution. To this solution was added 8.2 g of 4-bromoaniline (47 mmol) and a few pellets of 4-(dimethylamino)pyridine. The resulting slurry was treated with 20 mL of N,N-diisopropylethylamine (115 mmol) to afford a dark solution. After stirring for 2 hours at room temperature the reaction was quenched by the addition of H2O and diluted with additional CH2Cl2. The organic layer was washed with 1N HCl, saturated NaHCO3 solution, dried (Na2SO4), filtered, and concentrated in vacuo to afford crude N-(4-bromophenyl)-1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide as a dark brown syrup. The crude product was purified by silica gel flash chromatography on a 300 g column using gradient elution from 0% to 30% EtOAc/hexane. Most of the product-containing fractions were impure. All product-containing fractions were combined and concentrated in vacuo to afford a sticky orange foam. This material was further purified by silica gel flash chromatography on a 160 g column using gradient elution from 0% to 20% EtOAc/hexane. Appropriate fractions were combined and concentrated in vacuo to afford N-(4-bromophenyl)-1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide as a pale orange foam that was broken up to a powder. The material is not completely pure. Yield: 2.61 g (12% yield); 1H NMR (400 MHz, CDCl3): δ 7.64 (br s, 1H), 7.56-7.55 (impurity), 7.54-7.53 (m, 1H), 7.52-7.51 (m, 1H), 7.50-7.49 (impurity), 7.48-7.44 (m, 3H), 7.43-7.41 (m, 1H), 7.38-7.36 (m, 1H), 7.36-7.34 (m, 1H), 7.11 (s, 1H); GC/MS (EI, 70 eV) 445, 443.

Provenance & Evidence