反应详情

温度

85 °C

A mixture of (S)-2-(1-(2,8-dichloroquinolin-3-yl)ethyl)isoindoline-1,3-dione (0.5000 g, 1.347 mmol), 2-fluorobenzeneboronic acid (0.2073 g, 1.482 mmol), tetrakis(triphenylphosphine)palladium (0.07782 g, 0.06735 mmol), and sodium carbonate anhydrous (0.7138 g, 6.735 mmol) in acetonitrile-water (3:1) (12.00 mL, 1.346 mmol) was stirred at 85° C. After 28 h, the mixture was cooled to room temperature. The mixture was concentrated under reduced pressure to remove acetonitrile. The mixture was partitioned between CH2Cl2 (50 mL) and water (50 mL). The aqueous layer (pH 10˜11) was washed with CH2Cl2 (50 mL×2) to remove byproducts. The aqueous layer was treated with 2 N HCl (50 mL) and extracted with CH2Cl2 (50 mL×2). The combined organic layers were washed with water (50 mL×1), brine (50 mL×1), dried over Na2SO4, filtered, and concentrated under reduced pressure to give 2-(((S)-1-(8-chloro-2-(2-fluoro-phenyl)quinolin-3-yl)ethyl)carbamoyl)benzoic acid as a solid: LC-MS (ESI) m/z 448.9 [M+H]+. The crude product was carried on crude without purification for the next step.

1. temperaturethe mixture was cooled to room temperature
2. concentrationThe mixture was concentrated under reduced pressure
3. customto remove acetonitrile
4. customThe mixture was partitioned between CH2Cl2 (50 mL) and water (50 mL)
5. washThe aqueous layer (pH 10˜11) was washed with CH2Cl2 (50 mL×2)
6. customto remove byproducts
7. additionThe aqueous layer was treated with 2 N HCl (50 mL)
8. extractionextracted with CH2Cl2 (50 mL×2)
9. washThe combined organic layers were washed with water (50 mL×1), brine (50 mL×1)
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure