反应详情

温度

80 °C

A 2L vessel was charged with 3-Iodo-8-nitroquinoline (D3) (70.8 g, 236 mmol), copper (I) iodide (2.25 g, 11.8 mmol, 5 mol %), potassium phosphate (100 g, 472 mmol, 2 eq), ethylene glycol (0.71 L, 10 vol) and benzenethiol (36.2 ml, 354 mmol). The mixture was stirred and heated at 80° C. for 3.5 hours. The reaction mixture was cooled to 20° C. then H2O (700 ml) and dichloromethane (700 ml) were added, the mixture was stirred for 5 minutes then the lower organic layer was removed (contained solids). Charcoal (35.4 g, Norit SX) was added to the organic layer and the mixture was stirred at room temperature for 15 min then filtered through GF/F filter paper. The filter cake was rinsed with dichloromethane (140 ml) and the combined filtrate was washed with H2O (350 ml). The resulting dichloromethane solution was added to a suspension of magnesium monoperoxyphthalic acid hexahydrate (210 g, 424 mmol, 1.8 eq) in a mixture of dichloromethane (700 ml) and methanol (140 ml) over 45 minutes maintaining 18° C.<23° C. The resulting mixture was stirred rapidly for 2.25 hours at 20° C. to 23° C., then 10% w/v aqueous sodium sulfite (700 ml) was added over 15 minutes, the mixture was separated and treated with saturated aqueous sodium bicarbonate (280 ml). The mixture was stirred for 20 min before the layers were allowed to settle. The lower organic layer was removed, washed with water (280 ml), then concentrated at atmospheric pressure to ˜210 ml. The resulting mixture was cooled to 0° C., stirred for 2 hrs then filtered. The filter cake was washed with cold (0-5° C.) dichloromethane (70 ml) then dried in vacuo at 25 to 40° C. to give the title compound (D4) as a light yellow solid in 64-66% yield, identical spectroscopically to that prepared by the earlier method.

1. temperatureThe reaction mixture was cooled to 20° C.
2. stirringthe mixture was stirred for 5 minutes
3. customthe lower organic layer was removed (contained solids)
4. additionCharcoal (35.4 g, Norit SX) was added to the organic layer
5. stirringthe mixture was stirred at room temperature for 15 min
6. filtrationthen filtered through GF/F
7. filtrationfilter paper
8. washThe filter cake was rinsed with dichloromethane (140 ml)
9. washthe combined filtrate was washed with H2O (350 ml)
10. temperaturemaintaining 18° C.<23° C
11. stirringThe resulting mixture was stirred rapidly for 2.25 hours at 20° C. to 23° C.
12. additionwas added over 15 minutes
13. customthe mixture was separated
14. additiontreated with saturated aqueous sodium bicarbonate (280 ml)
15. stirringThe mixture was stirred for 20 min before the layers
16. customThe lower organic layer was removed
17. washwashed with water (280 ml)
18. concentrationconcentrated at atmospheric pressure to ˜210 ml
19. temperatureThe resulting mixture was cooled to 0° C.
20. stirringstirred for 2 hrs
21. filtrationthen filtered
22. washThe filter cake was washed with cold (0-5° C.) dichloromethane (70 ml)
23. customthen dried in vacuo at 25 to 40° C.