Methyl chloride Methyltestosterone

Alternatively, as described in U.S. Patent 3,341,557, 6-dehydro-17-methyltestosterone may be used as the starting material. A mixture of 0.4 g of cuprous chloride, 20 ml of 4 M methylmagnesium bromide in ether and 60 ml of redistilled tetrahydrofuran was stirred and cooled in an ice bath during the addition of a mixture of 2.0 g of 6-dehydro-l 7-methyl-testosterone, 60 ml of redistilled tetrahydrofuran and 0.2 g of cuprous chloride. The ice bath was removed and stirring was continued for four hours. Ice and water were then carefully added, the solution acidified with 3N hydrochloric acid and extracted several times with ether. The combined ether extracts were washed with a brine-sodium carbonate solution, brine and then dried over anhydrous magnesium sulfate, filtered and then poured over a 75-g column of magnesium silicate (Florisil) packed wet with hexanes (Skellysolve B). The column was eluted with 250 ml of hexanes, 0.5 liter of 2% acetone, two liters of 4% acetone and 3.5 liters of 6% acetone in hexanes. 

A solution of 1.0 g of crude 4,5-oxido-17a-methyltestosterone in 50 ml of methanol is allowed to stand at room temperature overnight with 10 ml of water and 1 ml of concentrated sulfuric acid. It is then poured into water containing sodium chloride and extracted three times with ethyl acetate. The solvent is washed with water, then with 10% sodium bicarbonate solution and again with water to neutrality. The residue remaining after evaporation of the solvent is crystallized from methanol, giving 17a-methyl-androstane-4p,5a,17p-triol-3-one with a melting point of 203°-205°C. 

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