Process for preparing (3α,5α)-3-hydroxy-3-methyl-pregnan-20-one (Ganaxolone)

A process for preparing (3α,5α)-3-hydroxy-3-methyl-pregnan-20-one (Ganaxolone), comprising the following steps:

• a) reaction of the compound (3β)-3-hydroxy-pregnan-20-one (Pregnanolone) with a glycol under acid catalysis conditions to obtain Pregnanolone 20,20′ ketal:
• b) oxidation of Pregnanolone 20,20′ ketal to obtain the corresponding Pregnane-3,20-dione 20,20′ ketal (Pregnanedione 20,20′ ketal):
• c) reaction of Pregnane-3,20-dione 20,20′ ketal with a methylmagnesium halide Grignard reagent, CH3MgX, to form (3α,5α)-3-hydroxy-3-methyl-pregnan-20-one 20,20′ ketal (Ganaxolone 20,20′ ketal):
• wherein the reaction takes place at a temperature between −35° C. and −15° C., X denotes a halogen atom selected from chlorine and bromine, and the reaction takes place in the presence of lithium and iron (III) salts with X anion;
• and
• d) deprotection of Ganaxolone 20,20′ ketal with iodine in a neutral environment to form Ganaxolone: