Patent GB-847713-A (GB)
Title: 19-nor-steroid compounds and process for the preparation thereof
IPC: C07J5/00
Filed: 1958-04-23
Abstract: The invention comprises (1) 19-nor-steroids of the formulae: <FORM:0847713/IV(b)/1> wherein R1 is H(OH) or = O, R is hydrogen or a carboxylic acid acyl group containing at most 10 carbon atoms and Y is hydrogen, methyl, ethyl or vinyl; (2) 19-nor-steroids of the formula: <FORM:0847713/IV(b)/2> wherein R1 is hydrogen or OH and R is H, OH or acyloxy, the acyl group being derived from a carboxylic acid of at most 10 carbon atoms; (3) D 4-11b  : 17a -dihydroxy-20-keto-19-nor-pregnene; and (4) a process for the preparation of 19-nor-steroids of the formula: <FORM:0847713/IV(b)/3> wherein R1 is H2, H(OH) or = O and R2 is (H) COCH3, (OH) COCH3, (H) COCH2OR3 (H) OR3 or (R4)OR3, R3 being hydrogen or an, acyl radial as defined above and R4 being methyl, ethyl or vinyl, comprising reacting a corresponding compound containing an acyloxy, alkyloxy, aryloxy or aralkyloxy group in the 3-position with an alkali metal in liquid ammonia or an aliphatic primary amine containing at most 6 carbon atoms, by which process the substituent in the 3-position is split off.  The reaction is advantageously carried out at below 0 DEG C. in a solvent such as an ether.  In examples (1) \se4-11b  : 17b -dihydroxy-3-keto-17a -methyl-19-nor-androstene is reduced to the corresponding 3-o1, this is converted to the 3-methyl ether, this is reduced by the process of the invention to \se4 - 11b  : 17b  - dihydroxy - 17a  - methyl-19-nor-androstene and this is converted into various 17-esters; (2) the corresponding 17a -vinyl compounds are prepared similarly via the 3-isopropyl ether, and \se4-3 : 11-diketo-17b -hydroxy-17a -ethyl-19-nor-androstene is similarly converted to \se4- 11 - keto - 17b  - hydroxy - 17a -ethyl-19-nor-androstene and esters thereof; (3) \se4-21-hydroxy-3 : 20-diketo-19-nor-pregnene is reduced to \se4-3 : 20 : 21-trihydroxy-19-nor-pregnene, this is converted to the tripropionyloxy compound, this is reduced by the process of the invention to \se4-20 : 21-dipropionyloxy-19-nor-pregnene, this is saponified to the 20 : 21-diol, this is converted to the 21-acetate, this is oxidized to \se4-hydroxy-20-keto-19-nor-pregnene-21-acetate and this is saponified to the 21-o1 and converted to various others esters;(4) D  4-11b  : 17a -dihydroxy-20-keto-19-nor-pregnene and \se4-17a  : 21-dihydroxy-20-keto-19-nor-pregnene are prepared similarly, except that the oxidation is performed on the 21-o1 to form the second named compound which is subsequently converted to various esters; (5) \se4-3 : 20-diketo-19-nor-pregnene is similarly converted to \se4-20-keto-19-nor-pregnene via the 3 : 20-dihydroxy compound and the 3-methyl ether thereof, and \se4-17a -hydroxy-3 : 20 diketo-19-nor-pregnene is similarly converted to \se4-17a -hydroxy-20-keto-19-nor-pregnene via the 3-triphenylmethyl ether; (6) \se4-17a  : 21-dihydroxy-3 : 11 : 20-triketo-19-nor-pregnene similarly gives a 3-methoxy-17a  : 20b  : 21-trihydroxy compound, this is treated by the process of the invention, the product is acetylated in the 21-position, the acetate is oxidized to \se4 - 17a : 21-dihydroxy-11 : 20-diketo-19-nor-pregnene-21-acetate which is either saponified and converted to various other esters or converted to the 20-mono-semicarbazone and then reduced and hydrolysed to give \se4-11b  : 17a  : 21-trihydroxy-20-keto-19-nor-pregnene-21-acetate which is subsequently hydrolysed to the 21-o1 and converted to various other esters; (7) \se4-17-hydroxy-3-keto-19-nor-androstene is converted to \se4-17b -hydroxy-19-nor-androstene via the 3 : 17-dihydroxy compound and the diacetate thereof; (8) \se4-3-keto-11b : 17b -dihydroxy-19-nor-androstene is reduced to the 3-o1, this is esterified to the 3 : 17b -dicyclopentylpropionate, this is reduced by the process of the invention and the product is saponified to give \se4 - 11b  : 17b -dihydroxy-19-nor-androstene and this is either converted to various esters or oxidized to \se4-11 : 17-diketo-19-nor-androstene; and (9) \se4-17b -hydroxy-17a -methyl-3-keto-19-nor-androstene is converted via the 3-ethyl ether to \se4-17b -hydroxy-17a -methyl-19-nor-androstene and the corresponding 17a -ethyl compound is similarly prepared.  In the general description the exemplified processes are referred to in more general terms and lists of etherifying and esterifying groups and reagents are provided.  The protection of keto groups by ketalization is also referred to.  Specifications 811,961 and 841,411 are referred to.