GB910118A - 6ª--methyl-16-alkylidene steroids - Google Patents

Abstract

The invention comprises (1) a process for the preparation of steroids of the formula <FORM:0910118/IV (b)/1> (wherein R is an acyl group of at most 6 carbon atoms and R1 is hydrogen or a methyl group) which comprises reacting a steroid of the formula <FORM:0910118/IV (b)/2> (wherein R11 is an alkyl group of at most 7 carbon atoms) with tetrabromomethane, tribromochloromethane, dibromodichloromethane or bromotrichloromethane under neutral or slightly alkaline conditions to give a steroid of the formula <FORM:0910118/IV (b)/3> (wherein X, X1 and X11 are bromine or chlorine), treating this with an organic base to give the corresponding 6-dihalomethylene steroid, reducing this in the absence of hydrogen ions to give a steroid of the formula <FORM:0910118/IV (b)/4> and treating this with an acidic or basic catalyst; and (2) the new steroid 17a -acetoxy-6a - methyl - 16 - ethylidenepregn - 4 - ene-3,20-dione. The addition of the halogenated methanes may be performed either in the presence of tertiary bases or in the presence of "acid abstractors" such as ethylene oxide or propylene oxide. The steroids of the last named general formula need not be isolated. Detailed examples are provided. 17a - Acetoxy - 3 - methoxy - 16 - methylenepregna-3,5-dien-20-one is prepared from the parent D 4-3-one and methyl orthoformate with methanol. 17a - Acetoxy - 16 - ethylidene - 3 - methoxypregna-3,5-dien-20-one is prepared by reacting 3-acetoxypregna-5,16-dien-20-one with diazoethane to give 3b -acetoxy-16,17-(11-methyl-21, 31-diazacyclopent-21-eno) - preg - 5 - en-20-one, heating this in dibutylether to give 3b -acetoxy-16-ethylpregna-5,16-dien-20-one, reacting this with alkaline hydrogen peroxide to give 16a ,17a - epoxy - 16b - ethyl-3b -hydroxypregn-5-en-20-one, and then either converting this to the 3-acetate, treating this with hydrogen bromide in acetic acid to give 3b -acetoxy-16-ethylidene - 17a - hydroxypregn - 5 - en-20-one, acetylating this to the 3,17-diacetate, hydrolysing this to the 3-ol-17-acetate, converting this by the Oppenauer method to 17a -acetoxy-16-ethylidenepregn-4-en-3,20-dione and reacting this with methyl orthoformate and methanol, or converting the 16b -ethyl-16a ,17a -epoxy-compound by the Oppenauer method to 16a ,17a - epoxy - 16b - ethyl - pregn-4-ene-3,20-dione, reacting this with acetic anhydride in presence of p-toluene sulphonic acid to give 3,17a - diacetoxy - 16-ethylidenepregn-3,5-dien-20-one and hydrolysing this to the D 4-3-one and converting this again to the 3-enol ether. In the Provisional Specification the group R is defined additionally as a hydrogen atom and the group R11 additionally as an alicyclic group. Specification 858,033 is referred to.