反应详情

To a solution of methyl 5-hydroxypyridine-2-carboxylate (0.273 g, 1.78 mmol) in DMF (6.84 mL) at room temperature was added sodium hydride (60% suspension in oil, 0.043 g, 1.78 mmol) and the resulting mixture was stirred at room temperature for 30 mins. After 30 min at room temperature 3-bromo-6-methoxy-2-(4-methoxyphenyl)benzothiophene 1-oxide (0.5 g, 1.37 mmol) was added and the reaction was heated to 80° C. for 18 h. Upon completion the reaction was cooled to room temperature, quenched with water and extracted with DCM. The organic layers were combined, passed through a phase separator and concentrated in vacuo to give the crude product, which was purified by column chromatography (SiO2, 0-75% EtOAc/heptane) to afford methyl 5-((6-methoxy-2-(4-methoxyphenyl)-1-oxidobenzo[b]thiophen-3-yl)oxy)picolinate (314 mg, 0.72 mmol, 52% yield). 1H NMR (400 MHz, CDCl3) δ ppm=3.73 (s, 3H), 3.84 (s, 3 H), 3.90-3.92 (m, 3 H), 6.79-6.86 (m, 2 H), 6.91 (dd, J=8.59, 2.53 Hz, 1 H), 7.03 (d, J=8.59 Hz, 1 H), 7.30 (dd, J=8.59, 3.03 Hz, 1 H), 7.48 (d, J=2.53 Hz, 1 H), 7.55-7.60 (m, 2 H), 7.95 (d, J=8.59 Hz, 1 H), 8.55 (d, J=2.02 Hz, 1 H), LC/MS (m/z, MH+): 438.2.

1. temperaturethe reaction was heated to 80° C. for 18 h
2. temperatureUpon completion the reaction was cooled to room temperature
3. customquenched with water
4. extractionextracted with DCM
5. concentrationconcentrated in vacuo
6. customto give the crude product, which
7. customwas purified by column chromatography (SiO2, 0-75% EtOAc/heptane)