Ethyl 4-bromo-3-methylthiophene-2-carboxylate → 1034981-21-9

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Reaction Conditions

Reaction Steps

A mixture of ethyl 5-bromo-3-methylthiophene-2-carboxylate and ethyl 4-bromo-3-methylthiophene-2-carboxylate (˜1:4) (7.12 g, 28.60 mmol) and copper cyanide (7.68 g, 85.79 mmol) in anhydrous N,N-dimethylformamide (50 mL) was stirred under nitrogen atmosphere at 150° C. for 5 h. The mixture was allowed to cool to ambient temperature, and then partitioned between ethyl acetate (200 mL) and 14% aqueous ammonium hydroxide (200 mL). The organic layer was washed with 14% aqueous ammonium hydroxide (2×100 mL) and brine (100 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The two regioisomers were separated by column chromatography eluted with 2% ethyl acetate in hexanes to afford the title compound as a colorless solid (0.42 g, 38%): 1H NMR (300 MHz, CDCl3) δ 7.39 (s, 1H), 4.36 (q, J=7.1 Hz, 2H), 2.55 (s, 3H), 1.38 (t, J=7.1 Hz, 3H); MS (ES+) m/z 196.1 (M+1).

Provenance & Evidence