反应详情

温度

27.5 °C

Under an argon atmosphere, a 50 wt % sodium hydroxide solution (67.7 g, 0.8462 mol) was added dropwise to a slurry of physostigmine salicylate (100 g, 0.2418 mol) in degassed DI water (300 mL) at 45° C. During the addition the temperature was kept between 45 and 55° C. After about 3 hours at 45° C. the yellow solution was cooled to 25 to 30° C. and tert.-butyl methyl ether (300 mL) was added. The pH of the aqueous phase was adjusted to 9.1 with an aqueous solution of sodium meta bisulfite (54 g, Na2S2O5, 250 mL water). The mixture was stirred for 30 minutes, the phases were allowed to settle and then separated. The aqueous phase was extracted twice for 30 minutes each with tert.-butyl methyl ether (300 mL each). The organic phases were combined and washed three times with 20 wt % sodium chloride solution (200 mL each), then dried over magnesium sulfate (150 g) overnight. The slurry was filtered through Celite and the filter cake washed with tert.-butyl methyl ether. The filtrate was concentrated to 300 mL at 25 to 29 in of vacuum and the residue co-distilled twice with diethoxymethane (300 mL each). The residue was diluted with diethoxymethane (300 mL) and heated to 50° C. The obtained light slurry was cooled to 5° C., stirred for 45 minutes, then concentrated to about 300 mL. Cold heptane (300 mL) was added dropwise, the slurry stirred for 20 minutes and the volume increased by addition of cold heptane (125 mL). After stirring for about 2 hours the slurry was filtered via a Buchner funnel. The collected solid was washed with cold heptane (200 mL) then dried in vacuo overnight. Eseroline base (35.6 g) was obtained as a white solid in 67.4% yield and 98.3% purity.

1. additionDuring the addition the temperature
2. customwas kept between 45 and 55° C
3. customseparated
4. extractionThe aqueous phase was extracted twice for 30 minutes each with tert.-butyl methyl ether (300 mL each)
5. washwashed three times with 20 wt % sodium chloride solution (200 mL each)
6. dry with materialdried over magnesium sulfate (150 g) overnight
7. filtrationThe slurry was filtered through Celite
8. washthe filter cake washed with tert.-butyl methyl ether
9. concentrationThe filtrate was concentrated to 300 mL at 25 to 29 in of vacuum
10. additionThe residue was diluted with diethoxymethane (300 mL)
11. temperatureheated to 50° C
12. temperatureThe obtained light slurry was cooled to 5° C.
13. stirringstirred for 45 minutes
14. concentrationconcentrated to about 300 mL
15. additionCold heptane (300 mL) was added dropwise
16. stirringthe slurry stirred for 20 minutes
17. temperaturethe volume increased by addition of cold heptane (125 mL)
18. stirringAfter stirring for about 2 hours the slurry
19. filtrationwas filtered via a Buchner funnel
20. washThe collected solid was washed with cold heptane (200 mL)
21. customthen dried in vacuo overnight