A process for the production of 17-‡-monoesters of 17-‡-hydroxy-20-keto-steroids

1,139,505. 17α - Monoesters of 17α - hydroxy- 20-keto-steroids. GLAXO LABORATORIES Ltd. 14 June, 1966 [23 June, 1965], No. 14091/65. Heading C2U. 17α-acyloxy-20-keto-21-unsubstituted pregnanes are prepared by heating the corresponding 21-iodo compounds with a tertiary amine or a dialkyl sulphoxide, or by heating the corresponding 21-hydrocarbonsulphonyloxy or 21- bromo compounds under similar conditions but with the addition of a metal iodide. An inert solvent may also be present. The acyl group is derived from an alkyl, cycloalkyl, cycloalkylalkyl or aralkyl group. The 21-bromo starting material may be prepared from the 21-hydrocarbonsulphonyloxy compound and an alkali metal or alkaline earth metal bromide under anhydrous conditions in a solvent, and the 21- iodo starting material may be prepared similarly using an alkali metal or alkaline earth metal iodide, or it may be prepared from the 21-bromo compound using the same reagent. The process is particularly applicable to the preparation of 17α-monoesters of 21-deoxybetamethasone and 21 -deoxydexamethasone. 21-Hydrocarbonsulphonyloxy starting materials are prepared from the 21-ols and hydrocarbon sulphonyl halides. 21 - Hydroxy - 16 - # - methyl - 17α - propionyloxypregna - 1,4,9(11) - triene - 3,20 - dione is prepared by reacting 17α,21 - dihydroxy - 16# - methylpregna - 1,4,9(11) - triene - 3,20 - dione with triethyl orthopropionate to give 16#- methyl - 17α,21 - (11 - ethyl - 11 - ethoxymethylenedioxy) - pregna - 1,4,9(11) - triene - 3,20 - dione and hydrolysing this. 9α - Fluoro - 11#,21 - dihydroxy - 16α - methyl - 17α - propionyloxy - pregna - 1,4 - diene - 3,20 - dione is prepared similarly via dexamethasone 17α,21-ethyl orthopropionate.