Ethyl isobutyrate → HCID 90011193, compound

Participants

Reaction Steps

To a freshly prepared solution of lithium diisopropyl amide (prepared by the addition of n-butyl lithium (12.27 mL, 19.63 mmol) to a solution of diisopropylamine (2.80 mL, 19.63 mmol) in THF (20 mL)) at −78° C., was drop-wise added a solution of ethyl isobutyrate (2.21 mL, 16.36 mmol) in THF (10 mL). The resulting mixture was stirred at the same temperature for 1 h and then the above prepared solution of 1-(5-bromopyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-3-carbonyl chloride (5.80 g, 16.36 mmol) in THF (20 mL) was drop-wise added. The resulting mixture was stirred at −78° C. for 30 min, then gradually warmed to room temperature over 1 h and then stirred for another 1 h at room temperature. The reaction was cooled to 0° C. and then quenched with saturated ammonium chloride solution (20 mL) and then diluted with ethyl acetate (100 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with brine (50 mL), dried (Na2SO4) and filtered. The filtrate was rotary evaporated and the crude product was purified by flash column chromatography (10% ethyl acetate in hexanes as eluent) to afford 2.50 g (35%) of the title compound as a white solid. 1HNMR (400 MHz, CDCl3) δ 8.58 (d, J=2.0 Hz, 1H), 8.02 (dd, J=2.0 & 8.0 Hz, 1H), 7.73 (d, J=8.0 Hz, 1H), 7.39 (s, 1H), 4.11 (q, J=7.0 Hz, 2H), 1.60 (s, 3H), 1.58 (s, 3H), 1.04 (t, J=7.0 Hz, 3H); ESI-MS (m/z) 434, 436 [(MH)+Br79,81].

Provenance & Evidence