Disiloxane → Prednisolone 17,21-diacetate

Participants

Reaction Steps

A mixture of 8 g of 11β -trimethylsiloxy-17α-hydroxy-21-acetoxy-pregna-1,4-diene-3,20 -dione (from Example 29), 8 g of paratoluenesulfonic acid monohydrate and 800 ml of isopropenyl acetate was allowed to stand for one week at room temperature. By this time TLC control indicated that almost all the starting material had reacted. 15 g of anhydrous sodium acetate was added and the mixture left stirring for another day. The supernatant was decanted from the salt crystals and the resulting solution -- after addition of 400 ml methyl-isobutyl ketone -- was washed twice, each time with 500 ml of water, then with 200 ml of saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to dryness. This residue was found to be 11β-trimethylsiloxy-17α,21-diacetoxypregna-1,4-diene-3,20-dione, about 90% pure, there was about 10% of a less polar artifact believed to be the result of a slight aromatization side reaction about ring A, followed by acetylation. The identity was proved by hydrolyzing off the silyl ether blocking group to give prednisolone 17,21-diacetate, identified by TLC with a sample obtained by the Ortho ester route.

Provenance & Evidence