反应详情

温度

60 °C

A round-bottom flask was charged with 7-bromo-4-chloro-3-nitroquinoline (1.083 g, 3.77 mmol, from Capot Chemical, Zhejiang, China), (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (0.911 g, 4.14 mmol), potassium carbonate (1.562 g, 11.30 mmol), and PdCl2(dppf) (0.138 g, 0.188 mmol). The flask was flushed with Ar (g), then 1,4-dioxane (9.42 ml) and water (3.14 ml) were added. The flask was fitted with a reflux condenser and lowered into a 60° C. oil bath for 45 min. The mixture was diluted with water and extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was taken up in 1,4-dioxane (9.42 ml). Xantphos (0.109 g, 0.188 mmol), Pd2(dba)3 (0.086 g, 0.094 mmol), n,n-diisopropylethylamine (1.316 ml, 7.53 mmol), and benzyl mercaptan (0.490 ml, 4.14 mmol) were added in sequence. The reflux condenser was attached, and the flask was heated to 60° C. for 2 h. The mixture was cooled to room temperature, diluted with EtOAc, then filtered through diatomaceous earth. The filtrate was concentrated, and the residue was purified by chromatography on silica gel (40-g column, 25-g silica gel loading column, 0 to 40% EtOAc/Heptane) to give 7-(benzylthio)-4-(2-methoxy-4-(trifluoromethyl)phenyl)-3-nitroquinoline (1.4698 g, 3.12 mmol, 83% yield) as a yellow solid. NMR indicated a 70:30 mixture of desired product to bis-coupling byproduct form the first step. m/z (ESI) 471.2 (M+H)+.

1. customThe flask was flushed with Ar (g)
2. addition1,4-dioxane (9.42 ml) and water (3.14 ml) were added
3. customThe flask was fitted with a reflux condenser
4. customlowered into a 60° C.
5. customfor 45 min
6. additionThe mixture was diluted with water
7. extractionextracted with EtOAc (2×)
8. dry with materialThe combined organic extracts were dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. temperatureThe mixture was cooled to room temperature
12. filtrationfiltered through diatomaceous earth
13. concentrationThe filtrate was concentrated
14. customthe residue was purified by chromatography on silica gel (40-g column, 25-g silica gel loading column, 0 to 40% EtOAc/Heptane)