反应详情

127.2 g (1.0 mol) of (R)-quinuclidinol was dissolved in 1270 mL of dichloromethane and then stirred at 25˜30° C. for 20 minutes to obtain a reaction solution. Subsequently, 472.9 g (1.2 mol) of bis(pentafluorophenyl)carbonate was added to the reaction solution to form a suspended reaction solution, and then the suspended reaction solution was stirred at 25˜30° C. for 3˜4 hours. After confirming the completion of a reaction using thin layer chromatography (TLC), 209.3 g (1.0 mol) of (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline was added to the reaction solution, and then stirred at 25˜30° C. for 4˜5 hours. After confirming the completion of a reaction using high performance liquid chromatography (HPLC), the reaction solution was concentrated under reduced pressure. Subsequently, 1270 mL water was added to the reaction solution, and concentrated hydrochloric acid was added dropwise into the reaction solution to adjust the pH of the reaction solution to 1˜2. Then, the reaction solution was washed with 1270 mL of toluene to remove pentafluorophenol (a by-product formed during the reaction) from the reaction product. Then, an aqueous layer was extracted from the reaction solution using 1270 mL of dichloromethane, and then the reaction solution was concentrated under reduced pressure. Then, 1270 mL of water was added to the reaction solution, the pH of the reaction solution was adjusted to 9˜10 using ammonium hydroxide, and then an aqueous layer was further extracted from the reaction solution using 1270 mL of toluene. Subsequently, 1270 mL of acetone and 118.1 g (1.0 mol) of succinic acid were added to the reaction solution, stirred at 55˜60° C. for 30 minutes, further stirred at 10˜15° C. for 2 hours, and then filtered to obtain a reaction product. Finally, the reaction product was washed with 640 mL of toluene and 640 mL of acetone, and then dried in vacuum at 40° C. to obtain 381.5 g (79.4%) of solifenacin succinate.

1. customto obtain a reaction solution
2. customto form
3. customa suspended reaction solution
4. customthe suspended reaction solution
5. stirringwas stirred at 25˜30° C. for 3˜4 hours
6. additionwas added to the reaction solution
7. stirringstirred at 25˜30° C. for 4˜5 hours
8. concentrationthe reaction solution was concentrated under reduced pressure
9. additionSubsequently, 1270 mL water was added to the reaction solution, and concentrated hydrochloric acid
10. additionwas added dropwise into the reaction solution
11. washThen, the reaction solution was washed with 1270 mL of toluene
12. customto remove pentafluorophenol (a by-product
13. customformed during the reaction) from the reaction product
14. extractionThen, an aqueous layer was extracted from the reaction solution
15. concentrationthe reaction solution was concentrated under reduced pressure
16. additionThen, 1270 mL of water was added to the reaction solution
17. extractionan aqueous layer was further extracted from the reaction solution
18. stirringstirred at 55˜60° C. for 30 minutes
19. stirringfurther stirred at 10˜15° C. for 2 hours
20. filtrationfiltered
21. customto obtain a reaction product
22. washFinally, the reaction product was washed with 640 mL of toluene and 640 mL of acetone
23. customdried in vacuum at 40° C.