反应详情

温度

40 °C

In a dark room, silver tosylate (3.5 g) was dissolved in water (˜100 mL) by sonication. The solution was heated to approximately 40° C. and additional water was added (˜15 mL). An equimolar amount of glycopyrrolate bromide (5 g) (mixture of R,S and S,R diastereomers) was added and immediately resulted in a yellow precipitate. The slurry was stirred at approximately 40° C. overnight, and then slowly cooled while stirring to ambient temperature. At ambient temperature, the solids were vacuum filtered and the wet cake was washed three times with approximately 10 mL of water. The mother liquor was collected and filtered two times through a 0.2 μm nylon filter with glass microfiber (GMF). A clear solution was observed after filtration and was lyophilized at approximately −50° C. After 6 days, a mixture of white, needle-like and slightly sticky, glassy solids was observed. Toluene (−20 mL) was added, and the slurry was briefly sonicated and then stirred at ambient temperature. Additional toluene (˜80 mL) was added for easier stirring, and the mixture was allowed to stand at ambient conditions for 1 day. Solids of glycopyrrolate tosylate were collected by vacuum filtration and vacuum drying at ambient temperature for 1 day.

1. customimmediately resulted in a yellow precipitate
2. temperatureslowly cooled
3. stirringwhile stirring to ambient temperature
4. customAt ambient temperature
5. filtrationfiltered
6. washthe wet cake was washed three times with approximately 10 mL of water
7. customThe mother liquor was collected
8. filtrationfiltered two times through a 0.2 μm nylon
9. filtrationfilter with glass microfiber (GMF)
10. filtrationafter filtration
11. customwas lyophilized at approximately −50° C
12. waitAfter 6 days
13. additiona mixture of white, needle-like
14. additionToluene (−20 mL) was added
15. customthe slurry was briefly sonicated
16. stirringstirred at ambient temperature
17. additionAdditional toluene (˜80 mL) was added
18. stirringfor easier stirring
19. waitto stand at ambient conditions for 1 day
20. filtrationSolids of glycopyrrolate tosylate were collected by vacuum filtration and vacuum
21. customdrying at ambient temperature for 1 day