Ethanol → Ethyl 6-bromoimidazo[1,2-a]pyridine-3-carboxylate

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Reaction Steps

To a suspension of 2-chloro-3-oxopropanoate potassium salt (6.3 g, 33 mmol) (prepared according to Ikemoto, T. et al., Tetrahedron 2000, 56, 7915-7921) and 2-amino-5-bromopyridine (1.93 g, 11.1 mmol) in ethanol (150 mL) was added concentrated sulfuric acid (1.1 g) and the reaction mixture was heated at reflux for 16 h, allowed to cool to ambient temperature and concentrated in vacuo. The residue was partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate (100 mL) and the aqueous phase was extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a 0-50% gradient of ethyl acetate in hexanes to afford ethyl 6-bromoimidazo[1,2-a]pyridine-3-carboxylate as a yellow solid in 48% yield (1.45 g): 1H NMR (300 MHz, CDCl3) δ9.48-9.42 (m, 1H), 8.26-8.19 (m, 1H), 7.63-7.55 (m, 1H), 7.49-7.40 (m, 1H), 4.45-4.31 (m, 2H), 1.44-1.31 (m, 3H); MS (ES+) m/z 268.9 (M+1), 270.9 (M+1).

Provenance & Evidence