Potassium Carbonate → 3-(Trifluoromethyl)pyrazole

Participants

Reaction Conditions

Reaction Steps

5-(5-bromothiophen-2-yl)-3-(trifluoromethyl)-1H-pyrazole (3.23 g, 10.88 mmol), prepared in a manner similar to that described in Example 1b, was dissolved in anhydrous DMF (40 mL). To this solution was added 2-chloro-5-(chloromethyl)thiophene (2.0 g, 11.97 mmol) and K2CO3 (2.25 g, 16.32 mmol). The reaction mixture was heated at 85° C. under nitrogen atmosphere for overnight. The solvent was evaporated and the resulting residue was taken into ethyl acetate. The reaction mixture was washed with water and brine and dried over anhydrous Na2SO4. It was concentrated in vacuo. The residue was purified by column chromatography (10% ethyl acetate in hexane), providing the product 5-(5-bromothiophen-2-yl)-1-(5-chlorothiophen-2-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole (1.39 g, 30%). 1H-NMR (CDCl3): δ 7.11 (m, 1H), 6.90 (m, 1H), 6.75 (m, 1H), 6.67 (m, 1H), 6.61 (s, 1H), 5.46 (s, 2H). The above product was coupled with an aryl boronic ester in a manner similar to that described in Example 1c, providing the title compound (161 mg, 45%). 1H-NMR (CDCl3): δ 7.63 (s, 1H), 7.50 (m, 1H), 7.40 (m, 2H), 7.32 (m, 1H), 7.12 (m, 1H), 6.74 (m, 1H), 6.69 (m, 1H), 6.66 (s, 1H), 5.54 (s, 2H), 1.66 (s, 6H). MS (ES): 511 [M+H]+.

Provenance & Evidence