反应详情

温度

-1 °C

4-Amino-5-chloro-2-methoxy benzoic acid methyl ester of Step A (5.00 g, 23.2 mmol) was suspended in water (52 mL) and concentrated sulfuric acid (13 mL) was added. The resulting suspension was cooled to −1° C. and a solution of sodium nitrite (1.76 g, 25.5 mmol) in water (10 mL) was added at a rate which maintained the temperature below 0° C., resulting in the formation of a clear yellow solution. A mixture of potassium iodide (4.23 g, 25.5 mmol) and iodine (3.24 g, 12.8 mmol) in water (50 mL) was then added dropwise and the reaction stirred at 0° C. for 1.5 hours. The reaction mixture was warmed to room temperature and extracted with ethyl acetate (200 mL). The combined extracts were washed sequentially with 1 M aqueous sodium thiosulfate, 1 N sodium hydroxide and brine, and dried over anhydrous magnesium sulfate, filtered and concentrated, whereupon the product crystallized. The resulting orange crystals were suspended in petroleum ether, filtered and dried in vacuo to provide the title compound (6.38 g), m.p. 72-73° C.

1. temperaturemaintained the temperature below 0° C.
2. customresulting in the formation of a clear yellow solution
3. additionwas then added dropwise
4. temperatureThe reaction mixture was warmed to room temperature
5. extractionextracted with ethyl acetate (200 mL)
6. washThe combined extracts were washed sequentially with 1 M aqueous sodium thiosulfate, 1 N sodium hydroxide and brine
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated, whereupon the product
10. customcrystallized
11. filtrationfiltered
12. customdried in vacuo