反应详情

A RBF was charged with 4-(benzylthio)-2-nitroaniline (13.72 g, 47.4 mmol), 1-bromo-2-fluoro-4-iodo-5-methoxybenzene (17.27 g, 52.2 mmol), Xantphos (1.372 g, 2.372 mmol), Pd2(dba)3 (1.086 g, 1.186 mmol), CPME (95 ml) and cesium carbonate (23.18 g, 71.2 mmol) were added. A reflux condenser was attached and the flask was lowered into a 90° C. heating bath. The mixture was stirred overnight. In the morning, the solid was scraped of the bottom of the flask, and an additional portion of cesium carbonate (23.18 g, 71.2 mmol) was added. The flask was returned to the heat with vigorous stirring for 3 h. After cooling, the mixture was diluted with EtOAc and filtered through celite with the aid of EtOAc. The filtrate was concentrated, and the residue was dissolved in DCM and loaded onto a pre-equilibrated 340-g SNAP Ultra column. The column was eluted with 0-30% EtOAc/Heptane. The material crashed out on the column, so the elution was changed to 0-50% EtOAc/Heptane with 10% DCM. The eluent was raised to 100% EtOAc, 20% DCM. Fractions containing product were combined and concentrated to give 22.96 g (>100% yield) of N-(4-(benzylthio)-2-nitrophenyl)-4-bromo-5-fluoro-2-methoxyaniline as a red solid that was 80-90% pure by LCMS. m/z (ESI) 563.0 (M+H)+.

1. additionwere added
2. customA reflux condenser was attached
3. customwas lowered into a 90° C.
4. temperatureheating bath
5. temperatureheat
6. stirringwith vigorous stirring for 3 h
7. temperatureAfter cooling
8. filtrationfiltered through celite with the aid of EtOAc
9. concentrationThe filtrate was concentrated
10. dissolutionthe residue was dissolved in DCM
11. washThe column was eluted with 0-30% EtOAc/Heptane
12. washso the elution
13. temperatureThe eluent was raised to 100% EtOAc, 20% DCM
14. additionFractions containing product
15. concentrationconcentrated