Sodium hydride → Ethyl 2-bromoimidazo[5,1-b]thiazole-7-carboxylate

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Reaction Steps

Ethyl isocyanoacetate (0.9 ml, 8.2 mmol) was gradually added dropwise to a suspension of sodium hydride (60% in mineral oil, 378 mg, 9.4 mmol) in N,N-dimethylformamide (5 ml) in an argon atmosphere under ice cooling. The mixture was stirred at the same temperature for 2 hr. This solution was added dropwise to a solution of 2,5-dibromothiazole (1.0 g, 4.1 mmol) in tetrahydrofuran (13 ml) cooled to −20° C. (brine/ice water) through a cannula over a period of 20 min, and, while allowing the temperature to rise to around 0° C., the mixture was stirred for 2 hr. After the completion of the reaction, saturated brine was added thereto, and the mixture was extracted with ethyl acetate (20 ml×5). The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure. The residue was washed with ethyl acetate to give ethyl 2-bromoimidazo[5,1-b]thiazole-7-carboxylate. The solvent was removed from the ethyl acetate washing liquor by distillation, and the residue was purified by chromatography on silica gel (hexane:ethyl acetate=1:2). The resultant purification product was combined with the crystal prepared above to give ethyl 2-bromoimidazo[5,1-b]thiazole-7-carboxylate (1.1 g, 90%) as a white solid.

Provenance & Evidence