Patent GB-1004463-A (GB)
Title: Process for the production of í¸-androstene and í¸-pregnene compounds
IPC: C07J75/00
Filed: 1962-05-21
Abstract: D 5 - 19 - Hydroxy or - 19 - acyloxy steroids of the androstane or pregnane series are prepared by treating the corresponding 5a -bromo-6b ,19-oxido-steroids with (a) metals with an oxidation potential of between +3.045 and +1.51 v. inclusive in solvents free from active hydrogen atoms; or (b) metals with an oxidation potential between +1.5 and +0.126 v. inclusive alone or in mixture with metals (a) in lower aliphatic alcohols or in liquid carboxylic acids of less than 12 carbon atoms; or (c) salts which on ionization give cations with an oxidation potential between +0.61 and +0.25 v. inclusive in lower aliphatic ketones or in lower aliphatic alcohols; or (d) metal iodides in lower aliphatic alcohols or ketones.  The products when acids are used as solvents are the corresponding 19-acylates, and, when other solvents are used, the free 19-ols.  In acidic or basic conditions the products are isomerized to D 4-compounds. Acylated products may be hydrolysed to free hydroxy steroids and protecting 17,20:20,21-bismethylenedioxy groups removed with acid. Examples are given, and the conversion of the products to 19-nor-steroids by the following routes is also described  <FORM:1004463/C2/1> 17,20:20,21 - Bismethylenedioxy - D 5 - pregnen - 3b  - ol - 11 - one acetate is prepared by reacting cortisone with formaldehyde to give 17,20:20,21 - bismethylenedioxy - D 4 - pregnene-3,11-dione, reacting this with acetic anhydride and acetyl chloride to give 3-acetoxy-17,20:20,21 - bismethylenedioxy - D 3,5 - pregnadien - 11 - one, reducing this with sodium borohydride to 17,20:20,21 - bismethylenedioxy - D 5 - pregnen - 3b  - ol - 11 - one and acetylating this.  Similarly are prepared 17,20:20,21 - bismethylenedioxy - D 4 - pregne - 3 - one, 3 - acetoxy - 17,20:20,21 - bismethylenedioxy - D 3,5 - pregnadiene and 17,20:20,21 - bismethylenedioxy - D 5 - pregnen - 3b  - ol and the acetate thereof.  5a  - bromo - 6b ,19 - oxido - androstan - 3,17-dione is prepared by reacting the diacetate of D 5 - androsten - 3b ,17b  - diol with N - bromo - acetamide to give 5a  - bromo - androstan-3b ,6b ,17b  - triol - 3,17 - diacetate, reacting this with lead tetraacetate to give the diacetate of 5a  - bromo - 6b ,19 - oxido - androstane - 3b ,17b -diol, hydrolysing this to the free diol, and oxidizing thio.  Similarly are prepared the 5a -bromo-6b ,19 - oxido - derivatives of pregnane - 3,20-dione, D 16 - pregnene - 3,20 - dione, 17,20; 20,21 - bismethylenedioxy - pregnane - 3,11-dione and 17,20;20,21 - bismethylenedioxy-pregnan - 3 - one via the corresponding intermediates; and, by similar methods, the 3,17-diacetate of 5a -bromo-pregnane-3b ,6b ,17a -triol-20 - one, the 3 - acetate of 16a  - methyl - 5a  - bromo - pregnane - 3b ,6b  - diol - 20 - one, the 3 - acetate of 16b  - methyl - 5a  - bromo - pregnane-3b ,6b -diol - 20 - one, the 3,17 - diacetate of 16a  - methyl 5a  - bromo - pregnane - 3b ,6b ,17a  - triol - 20 - one, the 3 - acetate of 16a ,17a  - isopropyl-idenedioxy - 5a  - bromo - pregnene - 3b ,6b  - diol -20 - one and the acetate of 5a  - bromo - androstane - 3b ,6b  - diol - 17 - one, and the corresponding 6b ,19-oxido-compounds.  3b  - acetoxy - 16b  - methyl - D 5 - pregnen - 20 - one and 3b  - acetoxy - 16a ,17a  - isopropylidenedioxy - D 5 - pregnen - 20 - one are prepared by acetylation of the 3b -ols. Specifications 966,099, 966,100, 966,101 and 966,102 are referred to.