Potassium Carbonate → 3-(Trifluoromethyl)pyrazole

Temperature

85 °C

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]+.

1. customThe solvent was evaporated
2. washThe reaction mixture was washed with water and brine
3. dry with materialdried over anhydrous Na2SO4
4. concentrationIt was concentrated in vacuo
5. customThe residue was purified by column chromatography (10% ethyl acetate in hexane)

ORD record

ord-8ee1cea07a5249fd94447921faea6458

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08703805B2