反应详情

温度

100 °C

To 1-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone (1G) (1.24 g, 4.12 mmol), ethyl 2-bromo-5-chlorothiazole-4-carboxylate (1I) (1.12 g, 4.12 mmol), lithium chloride (0.52 g, 12.4 mmol), tetrakis(triphenylphosphine)palladium (0.476 g, 0.412 mmol), and cesium carbonate (4.03 g, 12.4 mmol) was added 1,4-dioxane (30 mL) and water (10 mL). Nitrogen was bubbled through the reaction mixture for 5 minutes. The reaction mixture was heated to 100° C. and stirred overnight. The reaction mixture was cooled to rt, diluted with EtOAc, filtered through Celite, and concentrated under reduced pressure. To the crude residue was added EtOAc and water. The layers were separated and the aqueous layer was extracted with EtOAc and the combined organic extracts were washed sequentially with water, brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography on silica gel eluting with a gradient of 0 to 80% EtOAc in hexanes to provide 0.505 g (34%) of the desired product ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-chlorothiazole-4-carboxylate (1J): LC/MS (APCI): m/z 365.3 (M+H).

1. customNitrogen was bubbled through the reaction mixture for 5 minutes
2. temperatureThe reaction mixture was cooled to rt
3. additiondiluted with EtOAc
4. filtrationfiltered through Celite
5. concentrationconcentrated under reduced pressure
6. additionTo the crude residue was added EtOAc and water
7. customThe layers were separated
8. extractionthe aqueous layer was extracted with EtOAc
9. washthe combined organic extracts were washed sequentially with water, brine
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe crude residue was purified by column chromatography on silica gel eluting with a gradient of 0 to 80% EtOAc in hexanes