Patent GB-893141-A (GB)
Title: Improvements in or relating to steroids and the manufacture thereof
IPC: A47J36/34
Filed: 1958-05-23
Abstract: The invention comprises compounds of the general formulae <FORM:0893141/IV (b)/1> and <FORM:0893141/IV (b)/2> wherein X represents a keto or b -hydroxy group, Y represents hydrogen, fluorine, chlorine or bromine, Z represents a keto or b -hydroxy group or an acyloxy group derived from an organic carboxylic or sulphonic acid, and A represents a tertiary amino group of the general formula <FORM:0893141/IV (b)/3> wherein n and n1 represent 1 or 2, a process for the preparation of a compound of the second general formula above by reducing the corresponding 3-(N-cyclic tertiary amino)-6-methyl-11b -hydroxy-3,5-androstadiene-17-one with an alkali metal hydride such as lithium aluminium hydride, sodium hydride or sodium or potassium borohydride, a process for the preparation of 6a  - methyl - 11b , 17a  - dihydroxy - 4 - androsten - 3-one by hydrolysing a compound of the second general formula above in an aqueous medium with the optional further step of acylating the 17-hydroxy group with an organic carboxylic or sulphonic acid anhydride or halide (other acylating agents, such as isopropenyl acylate or ketene may be used) to form a 6a -methyl-11b ,17b -dihydroxy-4-androsten-3-one 17-acylate and with the optional further step of oxidizing the resulting 17-acylate with chromic acid (other oxidising agents, such as N-haloacid-amides and N-haloacidimides may be used) to form the corresponding 6a -methyl-17b -hydroxy - 4 - androstene - 3, 11 - dione 17 - acylate and, if desired, hydrolysing the 17-acylate to form 6a -methyl-17b -hydroxy-4-androstene-3, 11 - dione, a process for the preparation of 6a -methyl-11b -hydroxy-4-androstene-3,17-dione by hydrolysing in an aqueous medium a compound of the general formula <FORM:0893141/IV (b)/4> wherein A has the above significance, a process for the preparation of 6a -methyl-andrenosterone by oxidising 6a -methyl-11b -hydroxy-4-androstene - 3, 17 - dione, 6a  - methyl - 17b  - hydroxy - 4 - androstene - 3, 11 - dione or 6a  - methyl - 11b , 17b  - dihydroxy - 4 - androstene - 3 - one with chromic acid, a process for the preparation of a compound of the general formula <FORM:0893141/IV (b)/5> wherein Z represents a hydroxy or keto group, by treating the corresponding 11b -hydroxy compound with N-bromoacetamide and then with sulphur dioxide, a process for the preparation of a compound of the general formula <FORM:0893141/IV (b)/6> wherein Z represents a hydroxy or keto group and Y1 represents bromine or chlorine, by reacting the corresponding 9(11)-unsaturated compound free from a substituent at the 11-position with N-bromo- and N-chloro-acetamide in the presence of perchloric acid, with the optional further step of treating the product with potassium acetate to form a 9b ,11b -oxido compound of the general formula <FORM:0893141/IV (b)/7> wherein Z represents a hydroxy or keto group, and with the optional further step of treating the 9b ,11b -oxido compound with hydrogen fluoride to form a compound of the general formula <FORM:0893141/IV (b)/8> wherein Z has the same significance, a process for the preparation of 6a -methyl-9a -fluoro-17b -hydroxy-4-androstene-3, 11-dione or a 17-acylate thereof by acylating 6a -methyl-9a -fluoro-11b ,17b -dihydroxy-4-androstene-3-one, and then oxidising the 17b -acylate with chromic anhydride in acetic acid to form 6a -methyl-9a -fluoro-17b -hydroxy - 4 - androstene - 3, 11 - dione 17b  - acylate and, when required, hydrolysing to form the corresponding free 17b -hydroxy compound, and a process for the preparation of 6a -methyl-9a -fluoroadrenosterone by oxidizing 6a -methyl-9a  - fluoro - 17b  - hydroxy - 4 - androstene - 3,11-dione with potassium dichromate or by oxidising 6a  - methyl - 9a  - fluoro - 11b  - hydroxy - 4-androstene-3,17-dione with chromic anhydride in acetic acid. Detailed examples are given.  Specification 893,142 is referred to.ALSO:A pharmaceutical composition suitable for administration orally or by injection, especially as a suspension in an oil, contains as the active ingredient a steroid of the general formula <FORM:0893141/VI/1> wherein X represents a keto or b -hydroxy group, Y represents hydrogen, fluorine, chlorine or bromine, and Z represents a keto or b -hydroxy group or a b -acyloxy group derived from an organic carboxylic or sulphonic acid.  6a -Methyl - 11b  - hydroxy - testosterone or 6a -methyl - 11 - keto - testosterone may be incorporated into tablets together with hexyl barbital sodium. Specification 893,142 is referred to.