反应详情

To a heterogeneous mixture of physostigmine salicylate (450 g) in dichloromethane (1.35L) and water (1.35L) was added Na2CO3 (150 g) over 0.5-1.0 hour while maintaining 18°-20° C. During the addition the pH of the aqueous phase increases from 5.5 to 9.5. After stirring at 18°-20° C. for 0.5 hour the aqueous phase was separated and extracted with dichloromethane (2×112 mL). The combined dichloromethane phase was treated again with water (500 mL) and Na2CO3 (23 g) at 18°-20° C. and stiffed for 0.5 hour. The aqueous phase was separated, extracted with dichloromethane (2×112 mL) and the combined dichloromethane phases were washed with water (450 mL), dried over K2CO3 (20 g) and concentrated under reduce pressure below 30° C. to give 302 g of crystalline physostigmine free base (100.8% of theory, 99.0% HPLC purity).

1. temperaturewhile maintaining 18°-20° C
2. additionDuring the addition the pH of the aqueous phase
3. temperatureincreases from 5.5 to 9.5
4. customwas separated
5. extractionextracted with dichloromethane (2×112 mL)
6. additionThe combined dichloromethane phase was treated again with water (500 mL) and Na2CO3 (23 g) at 18°-20° C.
7. waitstiffed for 0.5 hour
8. customThe aqueous phase was separated
9. extractionextracted with dichloromethane (2×112 mL)
10. washthe combined dichloromethane phases were washed with water (450 mL)
11. dry with materialdried over K2CO3 (20 g)
12. concentrationconcentrated
13. custompressure below 30° C.