GB1438940A — 17beta-haloalkoxycarbonyl-17alpha-oxysteroids

USPTO Abstract

1438940 17# - Haloalkoxycarbonyl - 17α- acyloxy-steroids GLAXO LABORATORIES Ltd 17 July 1973 [19 July 1972] 33834/72 Heading C2U [Also in Division A5] Novel steroids of the formula (wherein X is H, C1 or F; R<SP>1</SP> is #-OH or oxo or, when X is Cl, it can also be #-C1; R<SP>2</SP> is H, =CH 2 or α- or #-CH<SP>3</SP>; R<SP>3</SP> is H or C 1 -C 4 alkyl; R<SP>4</SP> is fluoro-, chloro-, bromo- or iodo-methyl or fluoro-ethyl and #<SP>1</SP> is optional) are prepared by (i) esterifying the corresponding carboxylic acids; or (ii) acylating the corresponding 17α-ols; or (iii) reacting a corresponding steroid containing a 17#-sulphonyloxyalkyloxycarbonyl group with an alkali metal, alkaline earth metal or quaternary ammonium halide. In the products halogen atoms may be exchanged, an 11#-OH group may be oxidized to an 11-keto group and a #<SP>1</SP>-double bond may be hydrogenated. Starting materials of the above general formula wherein R<SP>4</SP> is H are prepared by method (ii) above using as starting materials the 17#- CO 2 H-17α-OH steroids. They are converted to their diethylamine and sodium salts by standard procedures. Chloromethyl 9α - fluoro - 11#,17α- dihydroxy - 16# methyl - 3 - oxo - androsta- 1,4 - diene - 17# - carboxylate is prepared by converting 9α - fluoro - 11#,17α - dihydroxy- 16# - methyl - 3 - oxo - androsta - 1,4 - diene- 17# - carboxylic acid to the sodium salt and then reacting this with chloromethyl iodide. 11#,17α - dihydroxy - 16α - methyl - 3 - oxoandrosta - 1,4 - diene - 17# - carboxylic acid is prepared by periodic acid oxidation of 16α- methylprednisolone. In one example a byproduct is 1<SP>1</SP>,1<SP>1</SP> - bis(9α fluoro - 11# - hydroxy- 16# - methyl - 3 - oxo - androsta - 1,4 - diene- 17-carbonyloxy)-methane. The novel steroids are anti-inflammatory agents and may be incorporated in pharmaceutical compositions (see Heading A5B). Specification 1,384,372 is referred to.