反应详情

温度

100 °C

(I13A): A round bottom flask was charged with tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (Intermediate 1) (5.39 g, 16.25 mmol), 4-((tert-butyldimethylsilyl)oxy)piperidine (3.5 g, 16.25 mmol), cesium carbonate (10.5 g, 32.5 mmol), Pd2(dba)3 (1.488 g, 1.625 mmol) and BINAP (1.012 g, 1.625 mmol) in toluene (54.2 ml). The flask was evacuated and purged with nitrogen (4×) and heated at 100° C. 2 d. After cooling to rt, the reaction mixture was diluted with ethyl acetate and vacuum filtered through a pad of Celite. The filtrate was concentrated in vacuo. The crude residue was purified by column chromatography on the Isco system (330 g, 60-95% CH2Cl2/Hex) to provide tert-butyl (3-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-2-chloro-5-cyanophenyl)carbamate (I13A) (3.27 g) as a yellow solid.

1. customThe flask was evacuated
2. custompurged with nitrogen (4×)
3. custom2 d
4. temperatureAfter cooling to rt
5. additionthe reaction mixture was diluted with ethyl acetate and vacuum
6. filtrationfiltered through a pad of Celite
7. concentrationThe filtrate was concentrated in vacuo
8. customThe crude residue was purified by column chromatography on the Isco system (330 g, 60-95% CH2Cl2/Hex)