Patent GB-877085-A (GB)
Title: Steroid compounds
IPC: C07J75/00
Filed: 1958-02-19
Abstract: The invention comprises 16a -methyl steroids of the general formula <FORM:0877085/IV (b)/1> wherein X represents hydrogen or a fluorine atom, Z represents a keto or b -hydroxy group, and R represents a hydroxy, phosphoryloxy or carboxylic acyloxy group, and the preparation of 16a -methyl-4-pregnene-11b ,17a ,21-triol-3,20-dione by reacting 16-pregnen-3a -ol-11,20-dione 3-acetate with methyl magnesium iodide in the presence of cuprous chloride to produce 16a -methyl - pregnan - 3a  - ol-11,20-dione 3-acetate, hydrolysing this compound to form 16a -methyl-pregnan-3a -ol-11,20-dione, reacting this compound with acetic anhydride in the presence of an acid catalyst to form a mixture of enol acetates including 16a -methyl-17(20)-pregnene-3a ,20-diol-11-one 3,20-diacetate, reacting the last mentioned compound with perbenzoic acid to form 16a -methyl-17a ,20-epoxypregnane-3a ,20-diol-11-one 3,20-diacetate, subjecting this compound to hydrolysis and brominating the resulting 16a -methylpregnane-3a -17a -diol-11,20-dione to form 21-bromo-16a -methylpregnane-3a ,17a -diol-11,20-dione, converting this compound to the corresponding 21-iodo compound with sodium iodide and the 21-iodo compound to 16a -methylpregnane-3a , 17a ,21-triol-11,20-dione 21-acetate with anhydrous potassium acetate, oxidising this compound with chromium trioxide in pyridine and brominating the resulting 16a -methylpregnane-17a ,21-diol-3,11,20-trione 21-acetate to produce 4 - bromo-16a -methylpregnane-17a ,21-diol-3,11, 20-trione 21-acetate, reacting the 4-bromo compound with semicarbazide to produce 16a -methyl - 4 - pregnene-17a ,21-diol-3,11,20-trione 3,20-bis-semicarbazone 21-acetate and either (a) hydrolysing this compound with alkali to form 16a  - methyl-4-pregnene-17a ,21-diol-3,11, 20-trione-3,20-bis-semicarbazone and then with acid to produce 16a -methyl-4-pregnene-17a ,21-diol-3,11,20-trione or (b) reacting it with sodium borohydride to produce 16a -methyl-4-pregnene-11b ,17a ,21-triol-3,20-dione 3,20-bis-semicarbazone and hydrolysing this compound with acid to produce 16a -methyl-4-pregnene-11b ,17a ,21-triol-3,20-dione.  The invention also includes the above process starting with either of the bromination steps; a process for the preparation of 16a -methyl-11-(keto or b -hydroxy)-4-pregnene-17a ,21-diol-3,20-dione 21-acetate by acetylating the corresponding 21-hydroxy compound which may optionally be prepared by any one of the processes previously referred to; a process for the preparation of 16a -methyl-9a -fluoro-4-pregnene-11b ,17a ,21-triol-3,20-dione 21-acetate by reacting 16a -methyl-4-pregnene-11b ,17a ,21-triol-3,20-dione 21-acetate (which may be prepared by the previous process) with methane sulphonyl chloride followed by potassium acetate or with phosphorus oxychloride to produce 16a  - methyl-4,9(11)-pregnadiene-17a ,21-diol-3,20-dione 21-acetate, reacting this compound with hypobromous acid to form 9a  - bromo - 16a -methyl-4-pregnene-11b ,17a ,21-triol-3,20-dione 21-acetate, reacting this compound with anhydrous potassium acetate to produce 16a -methyl-9,11-epoxy-4-pregnene-17a ,21-diol-3,20-dione 21-acetate, and converting this compound to 16a  - methyl-9a -fluoro-4-pregnene-11b ,17a ,21-triol-3,20-dione 21-acetate by treatment with hydrogen fluoride, and optionally oxidising this compound to 16a -methyl-9a -fluoro-4-pregnene-17a ,21-diol-3,11,20-trione 21-acetate with chromium trioxide; a process for the preparation of 16a -methyl-9a -fluoro-11-(keto or b -hydroxy)-4-pregnene-17a ,21-diol-3,20-dione by hydrolysing the corresponding 21-acetate which may be prepared by the process referred to above; and a process for the preparation of a 21-ester of 16a -methyl-9a -fluoro-11-(keto or hydroxy)-4-pregnene-17a ,21-diol-3,20-dione by sterifying the corresponding 21-hydroxy compound which may be prepared by a process referred to above. Detailed examples are given. Specification 877,087 is referred to.