Patent GB-929279-A (GB)
Title: Steroids and their production
IPC: C07J15/00
Filed: 1959-04-12
Abstract: <FORM:0929279/IV(a)/1> <FORM:0929279/IV(a)/2> <FORM:0929279/IV(a)/3> The invention comprises 10a -methyl-9b -steroid of the general formulae Z1a and Z2 shown in the Figure, wherein R1 represents a hydrogen atom or a methyl group, R2 represents none or one or more double bonds at one or more of positions 1, 2, 3, 4, 5, 6, 15 and 16, R3 represents a hydrogen atom or a methyl, ethyl, hydroxy, etherified hydroxy, or esterified hydroxy group, R4 represents a keto, hydroxy, etherified hydroxy or esterified hydroxy group, R5 represents a hydrogen or halogen atom, R6 represents a hydrogen or halogen atom or a hydroxy, etherified hydroxy or esterified hydroxy group, R7 represents a hydrogen or halogen atom, R8 represents a hydrogen atom or a hydroxy or keto group, R10 represents a hydrogen atom or a hydroxy, etherified hydroxy or esterified hydroxy group, Hlg represents a halogen atom, R represents an alkyl group, M represents a metal atom, and R11 represents a hydrogen atom or a hydroxy, etherified hydroxy or esterified hydroxy group; the preparation of the compounds of formula Z1a by condensing a corresponding 10a -methyl-9b -steroid of the general formula Z1 shown in the Figure with a dialkyl ester of oxalic acid in the presence of an alkali metal alkoxide under anhydrous conditions; and the preparation of the compounds of formula Z2 by treating the compounds of formula Z1a with molecular halogen, preferably bromine or iodine, in the presence of a solvent and decomposing the reaction product, for example, with an alkali metal alkoxide.  The reaction with the dialkyl oxalate may cause substitution at the 2- and/or 4-positions if these positions are unsubstituted, which results in 2- and/or 4-halogenated products being formed following the treatment with molecular halogen.  The halogen atoms may then be removed, for example, by treatment with zinc dust and glacial acetic acid.  The above processes may be modified in that the compounds of formula Z1 are prepared by oxidising the corresponding compound having attached to the 17-position the group of the formula -C(CH3)=CHD wherein D represents a secondary amine residue, an Oacyl group or a phenyl or C1 to C6 alkyl group, or of the formula -C(CH3)=CH(E)2 wherein each E represents a phenyl or C2 to C6 alkyl group. At any stage of the processes referred to above it is possible to introduce a D 1-double bond by dehydrogenation with iodine pentoxide, iodic acid, selenic acid or selenium dioxide, or by biochemical dehydrogenation or by dehydrohalogenation; to introduce at the 2-position an alkyl, halo, ester, hydroxy or ether substituent by reaction of a 3-ketone with an oxalic ester followed by either alkylation with an alkyl halide to form a 2-alkyl substituent or halogenation to form a 2-halo substituent which may then be converted to a 2-ester group, then hydrolysed to a 2-hydroxy group, and finally etherified to a 2-ether group; to introduce a D 6-double bond by allylic halogenation of a D 4-compound followed by dehydrohalogenation; to oxidise a 3-hydroxy group to a 3-keto group; or to esterify a 3-hydroxy group.  In the examples the sodium enolate of 21-ethoxy-oxalyl-lumiprogesterone and 21-iodo-lumi-progesterone are prepared.  Specification 929,272 also is referred to.