Patent GB-1055353-A (GB)
Title: Process for the preparation of 3-hydroxy-and 3-alkoxy-estratrienes and intermediates therefor
Inventor: ERCOLI ALBERTO
IPC: C07J5/00
Filed: 1963-12-19
Abstract: The invention comprises compounds of the Formulae I and II, wherein X2 represents a group of the Formula III or IV and a process for preparing compounds of the Formula V or VI, wherein X represents one of the groups of the Formula VII, lower alkyl and acyl radicals having 1 to 4 carbon atoms and the term lower alkynyl denotes ethynyl, and R represents an unsubstituted or hydroxy substituted saturated or unsaturated, straight or branched aliphatic hydrocarbon radical of 1 to 18 carbon atoms by reacting a compound of the Formula VIII or a compound of the Formula IX or a mixture thereof, when X1 represents one of the groups of the Formula X, wherein Z represents a ketonic oxygen atom or a C1- 14 alkylene ketal group with a mineral or organic acid having a pK of less than 1.5 m. solution in an inert, non-alcoholic organic solvent (when the 3-substituent of the product is -OH) or in an alcohol of the formula R-OH (when the 3-substituent of the product is -OR) and the preparation of compounds of the Formulae VIII and IX by epoxidation of the corresponding D 5(6) and D 5(10) steroids with a per acid or with hydrogen peroxide. <FORM:1055353/C2/1> <FORM:1055353/C2/2> <FORM:1055353/C2/3> <FORM:1055353/C2/4> <FORM:1055353/C2/5> <FORM:1055353/C2/6> <FORM:1055353/C2/7> <FORM:1055353/C2/8> <FORM:1055353/C2/9> <FORM:1055353/C2/100> 19 - Nor - 5(6) - androstene (and -5(10) - androstene) -3,17 - dione - 3,17 - bis - (ethylene ketal) are prepared by acetylating 3b ,17b -dihydroxy-5a  androstan-6-one, to give the 3b ,17b -diacetyloxy derivative reducing the latter with sodium borohydride to give the 3,17-diacetate of 5a -androstane 3b ,6b ,17b -triol which, with nitrosyl chloride gives 5a  - androstane - 3b ,17b  - diacetoxy - 6b  - yl nitrite, irradiating the latter with ultra-violet radiation to give the nitroso dimer corresponding to 19-oximino - 5a  - androstane - 3b ,6b ,17b  - triol,3,17-diacetate which is treated with phosphorus oxychloride to give 10b -cyano-19-nor-5-androstene-3b ,17b -diol, diacetate followed by hydrolysis to give 10b  - cyano - 19 - nor - 5 - androstene - 3b ,17b -diol which on treatment with chromic acid gives 10b  - cyano - 19 - nor - 5 - androstene - 3,17 - dione, converting the latter its 3,17-bis-(ethylene ketal) and treating with sodium metal in absolute ethanol.  In a similar manner to the above, 19-nor-5(6) (and 5(10)) - pregnene - 3,20 - dione, 3,20 - bis - (ethylene ketal) are prepared from the 3,20-diacetate of 5a -pregnane-3b ,20b -diol-6-one, via 5a -pregnane - 3b ,6b ,20b  - triol, 3,20 - diacetate; 3b , 20b  - diacetoxy - 5a  - pregnan - 6b  - yl - nitrite; the 3b ,20b  - diacetoxy - 19 - nitroso - 5a  - pregnan - 6b -ol dimer, together with 3b ,20b -diacetoxy-19-oximino -5a  - pregnan - 6b  - ol; 10b  - cyano - 19 - nor - 5 - pregnene - 3b ,20b  - diol - diacetate; 10b -cyano-19 - nor - 5 - pregnene - 3b ,20b  - diol; 10b  - cyano-19 - nor - 5 - pregnene - 3,20 - dione and 10b -cyano - 19 - nor - 5 - pregnene-3,20 -dione.  The D 5(6) and D 5(10) isomers of 17a -ethynyl-19-nor - androsten - 17b  - ol - 3 - one - 3 - ethylene ketal may be prepared from 10b -cyano-19-nor-5-androstene-3b ,17b -diol by reduction with cyclohexonone aluminium isopropoxide to give 10b -cyano - 19 - nor - D 4 - androstene - 3,17 - dione, conversion to the 3-ethylene ketal treatment with acetylene to give 10b -cyano-17a -ethynyl-19-nor-5-androsten - 17b  - ol - 3 - one - 3 - ethylene ketal followed by treatment with lithium in liquid ammonia.