反应详情

温度

100 °C

To a solution of sodium ethoxide 21% in ethanol (1.8 mL; 4.8 mmol) in dry ethanol (30 mL) under a nitrogen atmosphere was added (2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)(p-tolyl)methanone (1.09 g; 4 mmol) and diethyl succinate (0.929 mL; 5.6 mmol). The mixture was heated to 100° C. for 24 h. The reaction mixture was dissolved with water (8 ml) and acidified with a solution of hydrochloric acid 1N to pH 1 and the aqueous layer was extracted with ethyl acetate. The organics were combined, dried over sodium sulphate and concentrated under reduced pressure. The crude was suspended in dry ethanol (30 mL) and a catalytic amount of concentrated sulfuric acid (10 drops) was carefully added. The reaction mixture was heated to reflux for 21 h. The volatiles were removed under reduced pressure and the remaining residue was purified by flash-chromatography on silica gel using a gradient of methanol (1-20%) in ethyl acetate as eluent to furnish 0.358 g (19.6%) of ethyl[2-hydroxy-4-(p-tolyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetate as an ochre solid. ESI/APCI(+): 382 (M+H).

1. extractionthe aqueous layer was extracted with ethyl acetate
2. dry with materialdried over sodium sulphate
3. concentrationconcentrated under reduced pressure
4. additiona catalytic amount of concentrated sulfuric acid (10 drops) was carefully added
5. temperatureThe reaction mixture was heated
6. temperatureto reflux for 21 h
7. customThe volatiles were removed under reduced pressure
8. customthe remaining residue was purified by flash-chromatography on silica gel using a gradient of methanol (1-20%) in ethyl acetate as eluent