p-Toluenesulfonic acid → 21-Acetoxy-6-chloro-11beta-hydroxy-16alpha-methyl-4,6-pregnadiene-3,20-dione

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Reaction Steps

5.0 g. of 21-acetoxy-6α-chloro-11β-hydroxy-16α-methyl-4-pregnene-3,20-dione is combined with 45 ml. of ethylene glycol dimethyl ether, as well as 100 mg. of p-toluenesulfonic acid, and the mixture is stirred for 15 minutes at 10°-15°. Then, 18 ml. of ethanol is added thereto, and the mixture is combined with 3.1 ml. of triethyl ester of orthoacetic acid, and again agitated for 40 minutes at 20°-25°. The mixture is cooled to 10°, and a solution of 392 mg. of sodium acetate in 19 ml. of water is added dropwise thereto. The reaction solution is then brought to room temperature, combined with 7 ml. of dichloromethane as well as 30 ml. of water, and agitated for 20 minutes at 10°. The mixture is extracted several times with dichloromethane. The combined organic phases are washed with dilute sodium acetate solution. The product is concentrated under vacuum to 5 ml. and then 0.1 ml. of pyridine is added. The solution is diluted with 20 ml. of dioxane, combined with 2 ml. of water, as well as with 2.5 g. of dichlorodicyanobenzoquinone, and agitated for 80 minutes under ice cooling. One gram of sodium bisulfite, dissolved in 5 ml. of water, is added thereto and the mixture is concentrated under vacuum to 10 ml. and stirred into ice water. The mixture is agitated for one hour, the thus-obtained precipitate is filtered and washed with water. The moist residue is combined with 50 ml. of dichloromethane and stirred for 40 minutes at room temperature. This process is repeated once again. The dichloromethane solutions are washed with water, dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product, 6.2 g. of foam, is chromatographed on silica gel. With 55-67% ethyl acetate-hexane, 1.34 g. of 21-acetoxy-6-chloro-11β-hydroxy-16α-methyl-4,6-pregnadiene-3,20-dione is obtained after recrystallization from acetonediisopropyl ether; m.p. 171° [α]D25 =+176° (methanol). UV: ε285 =17,800 (methanol).

Provenance & Evidence