Acetic Anhydride → 2beta-(4-Morpholinyl)-16beta-(1-pyrrolidinyl)-5alpha-androstane-3alpha,17beta-diol 17-acetate

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

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).

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