反应详情

A mixture of 3-amino-2-thiophenecarboxylic acid (8 g, 49 mmol), ethyl 4-fluorobenzoylacetate (9.6 g, 49 mmol), and p-toluenesulfonic acid monohydrate (0.2 g, 1 mmol) in toluene (100 mL) is refluxed for 20 hours with a Dean-Stark water trap to remove produced water. After cooling to room temperature, the precipitate is filtered and washed with diethyl ether. The solid is dissolved in diphenyl ether (80 mL) and heated at 220° C. for 2 hours. The reaction solution is then cooled to room temperature, diethyl ether is added, and the precipitate is filtered and washed with diethyl ether to give 5-(4-fluorophenyl)-thieno[3,2-b]pyridin-7-ol (2 g, 17% yield) as brown crystalline needles, m.p. 316-318° C.

1. customto remove
2. customproduced water
3. filtrationthe precipitate is filtered
4. washwashed with diethyl ether
5. dissolutionThe solid is dissolved in diphenyl ether (80 mL)
6. temperatureheated at 220° C. for 2 hours
7. temperatureThe reaction solution is then cooled to room temperature
8. additiondiethyl ether is added
9. filtrationthe precipitate is filtered
10. washwashed with diethyl ether