Osmium tetroxide Cortisone acetate

Hydroxycortisone BMD) (48) A solution of 4 g of 17a,20 20,21-bis-methylenedioxypregn-4-ene-3,l 1-dione (cortisone BMD) (46) dissolved in 300 ml of t-butanol and 5 ml of water is treated with 34 ml of 35 % hydrogen peroxide and 0.45 g of osmium tetroxide predissolved in 36 ml of /-butanol. The resulting mixture is allowed to stand at room temperature for 2 days. Diol (47) which crystallizes during the reaction is collected by filtration and washed with /-butanol and water. The filtrate is diluted with ethyl acetate and washed sequentially with aqueous sodium chloride, aqueous 10% sodium bisulfite, aqueous 10% sodium bicarbonate and finally with water to neutrality. The solvent is evaporated and a second crop of the diol (47) is collected, providing a total of about 3.8 g. 

A solution of 1.0 g of A -3,11-diketo-20-cyano-21-acetoxy-pregnene in 10 cc of benzene is treated with 1.0 g of osmium tetroxide and 0.43 g of pyridine. After standing at room temperature for 18 hours, the resulting solution is treated successively with 50 cc of alcohol, and with 50 cc of water containing 2.5 g of sodium sulfite. The mixture is stirred for 30 hours, filtered, and the filtrate acidified with 0.5 cc of acetic acid and concentrated to small volume in vacuo. The aqueous suspension is then extracted four times with chloroform, the chloroform extracts are combined, washed with water and concentrated to dryness in vacuo. Recrystallization of the residue from acetone gives 3,11,20-triketo-17(a)-21-dihydroxy-pregnane MP 227° to 229°C. This compound is then treated with acetic anhydride and pyridine for 15 minutes at room temperature to produce 3,11,20-triketo-17(a)-hydroxy-21-acetoxy-pregnane or cortisone acetate. 

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