Triethylamine → 4-Oxazolecarboxylic acid, 5-[4-(trifluoromethyl)phenyl]-, ethyl ester

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Reaction Steps

Triethylamine (10.0 mL, 71.9 mmol) was added to a solution of 4-(trifluoromethyl)benzoyl chloride (5.0 g, 24.0 mmol) in THF (50 mL) at 0° C. Ethyl 2-isocyanoacetate (2.9 mL, 26.4 mmol) was added dropwise and the mixture was warmed to ambient temperature. After 3.5 days the reaction mixture was partitioned between EtOAc (100 mL) and H2O (100 mL). The separated aqueous phase was extracted with EtOAc, and the combined organic layer was washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Chromatography on silica gel (Analogix® Intelliflash 280™; SF40-150 g column; 20% to 50% EtOAc/hexanes eluant, 30 min) yielded 4.30 g (63%) of the title compound as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 8.66 (s, 1H), 8.18 (d, J=8.2, 2H), 7.92 (d, J=8.3, 2H), 4.31 (q, J=7.1, 2H), 1.28 (t, J=7.0, 3H). MS (DCI+) m/z 286 (M+H).

Provenance & Evidence