反应详情

温度

58 °C

In a 0.25 L three-necked round bottom flask equipped with a mechanical stirrer, a condenser and thermometer, 25 g of desmethyl-azithromycin was dissolved in 102 mL of acetone. Formaldehyde (5.3 mL) and formic acid (2.6 mL) were added and the clear solution was heated to reflux (˜58° C.). The mixture was maintained under reflux for 3 hours then cooled to less than 40° C. and 102 mL of water was added. The acetone was separated from the reaction mixture by distillation under low vacuum (˜300 mbar). The distillation was stopped when the temperature of the liquid phase reaches ˜40° C./300 mbar. Activated carbon SXI (1.25 g) was added and the suspension was mixed for 1 hour. Then the activated carbon was separated from the solution by filtration on a Büchner filter containing Hyflow. The filter cake was washed with 102 mL of water. The pH was adjusted with an NaOH solution of 47% to 10-10.5 (˜3.14 g). A massive precipitation of Azithromycin was observed. After stirring the suspension for 1 hour, the crude azithromycin was separated by filtration, washed twice with 25 mL of water and dried at 40° C. in a vacuum oven for>24 hours. After drying, 19.7 g of crude azithromycin was obtained (yield 77% based on weight). No impurities that were derivatives of azithromycin were detected.

1. customIn a 0.25 L three-necked round bottom flask equipped with a mechanical stirrer, a condenser
2. temperaturethe clear solution was heated
3. temperatureThe mixture was maintained
4. temperatureunder reflux for 3 hours
5. temperaturethen cooled to less than 40° C.
6. customThe acetone was separated from the reaction mixture by distillation under low vacuum (˜300 mbar)
7. distillationThe distillation
8. customreaches ˜40° C.
9. additionActivated carbon SXI (1.25 g) was added
10. additionthe suspension was mixed for 1 hour
11. customThen the activated carbon was separated from the solution by filtration on a Büchner
12. filtrationfilter
13. additioncontaining Hyflow
14. washThe filter cake was washed with 102 mL of water
15. customA massive precipitation of Azithromycin
16. customthe crude azithromycin was separated by filtration
17. washwashed twice with 25 mL of water
18. customdried at 40° C. in a vacuum oven for>24 hours
19. customAfter drying