反应详情

温度

2.5 °C

To a suspension of 2β-(4-morpholinyl)-16β-(1-pyrrolidinyl)-5α-androstan-3α,17β-diol (2.067 Kg, 4.628 mol) in dichloromethane (103.35 L) at 20-22° C., was added triethylamine (1.935 L, 13.883 mol) under N2 atmosphere. The mixture was stirred until complete dissolution. Acetic anhydride (0.873 L, 9.255 mol) was charged slowly under continuous stirring and then the resulting reaction mixture was stirred for 22 h at a temperature of 20-22° C. A 5% Na2CO3 solution (41.34 L) was then added and the mixture was stirred for 5-10 min. The phases were separated and the organic phase was washed with water (2×41 L) at 15° C., dried with anhydrous Na2SO4 (10 Kg), and filtered under vacuum to remove salts, which were rinsed with dichloromethane (10 L). The solvent was removed under vacuum at a temperature lower than 20° C. until a final volume of 12 L was obtained. To the concentrated stirred solution at a maximum temperature of 20° C. was added wet acetonitrile (40 L), followed by concentrating under vacuum at a temperature lower than 15° C., to a total volume of 40 L of a suspension. The resulting suspension was cooled to 0-5° C., stirred for 1 h, filtered off under vacuum and washed with acetonitrile (3 L). The desired wet product was dissolved in dichloromethane (9.5 L) at 20-22° C., followed by addition of acetonitrile (38 L). The volume was reduced under vacuum at a temperature lower than 15° C. to a total volume of 39 L to give a suspension. The resulting suspension was cooled to 0-5° C. and stirred for 1 h. The obtained solid was filtered off under vacuum and the product was washed with acetonitrile (3 L). The pure product was dried in a vacuum oven at 40° C. for at least 15 h to give 1.51 Kg of a white solid. (68.8% molar yield and a purity of 99.9% by HPLC); M.P. 160° C.; [α]D20+55.5 (c=1.0 in CHCl3).

1. stirringunder continuous stirring
2. customthe resulting reaction mixture
3. stirringwas stirred for 22 h at a temperature of 20-22° C
4. stirringthe mixture was stirred for 5-10 min
5. customThe phases were separated
6. washthe organic phase was washed with water (2×41 L) at 15° C.
7. dry with materialdried with anhydrous Na2SO4 (10 Kg)
8. filtrationfiltered under vacuum
9. customto remove salts, which
10. washwere rinsed with dichloromethane (10 L)
11. customThe solvent was removed under vacuum at a temperature lower than 20° C. until a final volume of 12 L
12. customwas obtained
13. stirringTo the concentrated stirred solution at a maximum temperature of 20° C.
14. concentrationby concentrating under vacuum at a temperature lower than 15° C., to a total volume of 40 L of a suspension
15. stirringstirred for 1 h
16. filtrationfiltered off under vacuum
17. washwashed with acetonitrile (3 L)
18. dissolutionThe desired wet product was dissolved in dichloromethane (9.5 L) at 20-22° C.
19. additionfollowed by addition of acetonitrile (38 L)
20. customwas reduced under vacuum at a temperature lower than 15° C. to a total volume of 39 L
21. customto give a suspension
22. temperatureThe resulting suspension was cooled to 0-5° C.
23. stirringstirred for 1 h
24. filtrationThe obtained solid was filtered off under vacuum
25. washthe product was washed with acetonitrile (3 L)
26. customThe pure product was dried in a vacuum oven at 40° C. for at least 15 h