反应详情

5-Chloro-2-iodobenzoic acid (2.8 g, 10 mmol) was taken up in dry methylene chloride (80 mL) and DMF (50 μL, cat.) followed by thionyl chloride (2.4 g, 20 mmol) were added. The mixture was stirred at reflux for 12 h, cooled to room temperature and evaporated in vacuo. The residue was azeotroped with toluene (2×10 mL) and used without further purification. The 5-chloro-2-iodobenzoyl chloride (10 mmol) was taken up in dry methylene chloride (50 mL) and N,O-dimethylhydroxylamine hydrochloride (1.1 g, 11 mmol) was added. The mixture was cooled to 0° C., and pyridine (2.4 g, 30 mmol) was added. The mixture was allowed to warm to room temperature, stir for 12 h, and was then quenched with saturated brine (20 mL). The organic phase was separated and the water phase was extracted with methylene chloride (2×10 mL). The combined organic extracts were dried with anhydrous MgSO4, filtered and evaporated in vacuo. The residue was purified using flash chromatography on silica gel (50 g) using methylene chloride as eluent to provide 5-chloro-2-iodo-N-methoxy-N-methylbenzamide (3.1 g, 95%) MS m/z=326 (M+H).

1. additionwere added
2. temperatureat reflux for 12 h
3. customevaporated in vacuo
4. customThe residue was azeotroped with toluene (2×10 mL)
5. customused without further purification
6. temperatureThe mixture was cooled to 0° C.
7. temperatureto warm to room temperature
8. stirringstir for 12 h
9. customwas then quenched with saturated brine (20 mL)
10. customThe organic phase was separated
11. extractionthe water phase was extracted with methylene chloride (2×10 mL)
12. dry with materialThe combined organic extracts were dried with anhydrous MgSO4
13. filtrationfiltered
14. customevaporated in vacuo
15. customThe residue was purified