5alpha-Dihydroprogesterone → Ganaxolone

Participants

Reaction Steps

5α-Pregnane 3,20-dione (10 g) is reacted with a reagent obtained by reacting FeCl3 (5.2 g) and MeMgCl (4 equiv, based on FeCl3) in t-butyl methyl ether (anhydrous, 200 mf) at −25° C. for 3h. The reaction is quenched with acetic acid (32 ml). The reaction mixture is concentrated in vacuo and the residue is stirred with 3N HCI for 6 h. The solid is collected by filtration, washed with water and dried at 50° C. under vacuum to obtain crude ganaxolone. The crude product is dissolved in THF (33 mL) at reflux and filtered not. The filtrate is added with water (45 mL) to obtain a suspension, which is collected by filtration, washed with water and dried. The dried product is further slurried in ethyl acetate (50 mL) at 70° C. for 19 h, The suspension is cooled to 0° C. and filtered. The ethyl acetate slurry step was repeated second time to obtain purified ganaxolone.

Provenance & Evidence