Patent GB-832244-A (GB)
Title: Improvements in or relating to steroid compounds
IPC: C07J75/00
Filed: 1956-12-11
Abstract: The invention comprises 17a -hydroxy- D 1,4-pregnadiene-3,11,20-trione and 2a ,4b -dibromo-17a  - hydroxy - 21 - acetoxy - pregnane - 3,20 - dione, and a process for the preparation of 3-keto- D 1,4-steroids by treating 3-keto-steroids having at ring A the general formula <FORM:0832244/IV (b)/1> wherein X and X1 represent the same or different halogen atoms, with lithium halide and lithium carbonate, using a disubstituted amide of a fatty acid containing up to 14 carbon atoms as the reaction solvent, at an elevated temperature, e.g. at a temperature of from 70 DEG  C. to the boiling temperature of the reaction mixture.  The lithium halide may be the bromide, chloride or iodide.  The lithium carbonate and the lithium halide may be present in an amount of at least 1/10 molecule and 1/5 molecule respectively for each molecule of dihalogenated ketosteroid, a preferred proportion being 1/10 to 1 molecule of lithium halide and more than 1 molecule of lithium carbonate for each molecule of dihalogenated steroid.  The lithium halide may be formed by the action of lithium carbonate on the di-halogenated steroid, the amount of said carbonate being about equal to the weight of said steroid.  The disubstituted amide solvent is preferably an alkyl disubstituted amide containing less than 14 carbon atoms, e.g. dimethylformamide, diethylformamide or dimethylacetamide.  The 3-keto-steroids having at ring A the above general formula may belong to the normal or allo series such as an androstane, etiocholane, pregnane or allopregnane.  These keto steroids may contain other substituents in the B, C and D rings, e.g. free or esterified hydroxy groups, free or protected carbonyl groups, and, when they belong to the pregnane or allopregnane series, the side chain may contain a carbonyl or enol ester group at the 20-position, or a free or halogenated methyl group or an acyloxygroup in the 21-position.  In the examples: the 17-benzoate and acetate of D 1,4 - androstadiene - 17b  - ol - 3 - one is prepared from the 17-benzoate of 2,4-dibromo-androstane - 17b  - ol - 3 - one and 2,4 - dibromo - 17b - acetoxy - etiocholane - 3 - one respectively, D 1,4 - androstadiene - 3,17 - dione is prepared from 2,4 - dibromo - androstane - 3,17 - dione, 17a  - hydroxy - D 1,4 - pregnadiene - 3,11,20 - trione is prepared from 2,4-dibromo-17a -hydroxy-pregnane-3,11,20-trione, the acetate of D 1-dehydrocortisone is prepared from 2a ,4b -dibromo - 17a  - hydroxy - 21 - acetoxy - pregnane-3,11,20-trione, 21-acetoxy-17a -hydroxy-D 1,4-pregnadiene-3,20-dione is prepared from 2a ,4b  - dibromo - 17a  - hydroxy - 21 - acetoxy - pregnane-3,20-dione and is then saponified to the free 21-hydroxy compound, the acetate of D 1-dehydrocortisol is prepared from 2a ,4b -dibromo - 11b ,17a  - dihydroxy - 21 - acetoxy - pregnane-3,20-dione, and 21-bromo-17a -hydroxy - D 1,4 - pregnadiene - 3,11,20 - trione is prepared from 2a - and 2b -, 4b ,21-tribromo-17a  - hydroxy - pregnane - 3,11,20 - trione.  The examples also refer to dehydrogenation processes using lithium bromide or chloride alone which gives rise to compounds having D 4,6-unsaturation as well as compounds having D 1,4-unsaturation. Thus in the dehydrobromination of the 17-benzoate of 2,4-dibromo-androstane-17b -ol-3-one and 2a ,4b -dibromo-17a -hydroxy-21-acetoxy-pregnane-3,11,20-trione with lithium bromide some 17-benzoate of D 4,6-androstadiene-17b -ol-3-one and the acetate of D 6-dehydrocortisone respectively are formed, and in the dehydrobromination of 2,4-dibromo-androstane-3,17-dione and of the 17-acetate of 2,4-dibromo-etiocholane-17b -ol-3-one with lithium chloride some D 4,6-androstadiene-3,17-dione and the 17-acetate of D 4,6-androstadienolone respectively are formed. p   The 17-acetate of 2 - bromo - D 1 - etiocholene - 17b -ol-3-one is also obtained when the 17-acetate of 2,4-dibromo-etiocholane-17b -ol-3-one is dehydrobrominated with lithium chloride.  2a ,4b  - Dibromo - 11b ,17a  - dihydroxy - 21 - acetoxy-pregnane-3,20-dione is prepared by brominating 17a  - hydroxy - 21 - acetoxy - pregnane - 3,20 - dione or 4 - bromo - 17a  - hydroxy-21-acetoxy-pregnane-3,20-dione with bromine and hydrobromic acid in dioxan.  The 17 - acetate of 2,4 - dibromo - etiocholane-17b -ol-3-one is prepared by heating 3a -hydroxy-17b -acetoxy-etiocholane dissolved in benzyl alcohol with N-bromo-succinimide.  Specifications 760,362, 816,909, 817,175, 828,601 and 828,602 are referred to.