Water → methyl 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-2H-tetrazol-2-yl]ethyl}-1H-pyrazole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

51.5 mg (2.14 mmol) of sodium hydride were initially charged in 15 ml of tetrahydrofuran, and a solution of 1380 mg (2.32 mmol) of a 25% strength solution of 5-(trifluoromethyl)-2H-tetrazole in tetrahydrofuran was added at 0° C. After 20 minutes of stirring at 0° C., 500 mg (1.78 mmol) of methyl 1-(3-chloropyridin-2-yl)-3-(oxiran-2-yl)-1H-pyrazole-5-carboxylate were added, and the mixture was stirred at reflux temperature for 20 hours. The reaction mixture was poured into water, acidified with glacial acetic acid and then extracted repeatedly with ethyl acetate. The combined organic phases were washed with water and then dried over magnesium sulphate. The solvent was distilled off under reduced pressure and the residue was chromatographed on silica gel, which gave 286 mg (80% of theory) of methyl 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-2H-tetrazol-2-yl]ethyl}-1H-pyrazole-5-carboxylate and methyl 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-1H-tetrazol-1-yl]ethyl}-1H-pyrazole-5-carboxylate in a ratio of 66:34. (logP: 2.64/2.68; MH+: 418.0; 1H-NMR (400 MHz, CD3CN, δ, ppm): 3.73 (s, 3H), 4.31 (m, 2H), 4.48 (m, 1H), 7.10 (m, 1H), 7.54 (m, 1H), 8.05 (m, 1H), 8.50 (m, 1H).)

Provenance & Evidence