5alpha-Dihydroprogesterone → Ganaxolone

Participants

Reaction Conditions

Reaction Steps

Ferrous chloride (4 g) is reacted with MeLi (3 equiv. based on FeCl2) in toluene (anhydrous, 200 mL) at −25° C. under nitrogen. 5α-pregnane 3,20-dione (10 g) is then added to this mixture. The mixture is stirred at −25° C. for 5 h. It is quenched by adding acetic acid (32 mL). The mixture is concentrated in vacuo and the residue is stirred in 3N HCl (200 mL) for 6 h. The solid is collected by filtration, washed with water and dried. The crude product is dissolved in THF (33 mL) at reflux and filtered hot. The filtrate is mixed with water (45 mL) and the solid is collected by filtration, washed with water and dried. The solid is further slurried in ethyl acetate (50 mL) at 70° C. for 8 h. It is cooled to 5° C. and filtered, washed with cold ethyl acetate and dried to obtain ganaxolone.

Provenance & Evidence