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

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).

1. temperaturethe reaction mixture was heated
2. temperatureat reflux for 16 h
3. concentrationconcentrated in vacuo
4. customThe residue was partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate (100 mL)
5. extractionthe aqueous phase was extracted with ethyl acetate (2×50 mL)
6. washThe combined organic phases were washed with brine (50 mL)
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was purified by column chromatography
11. washeluting with a 0-50% gradient of ethyl acetate in hexanes

ORD record

ord-7f024c67c4ca4b77bb3a58d89c9d43e5

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365578B2