Patent ES-379196-A1 (ES)
Title: 01beta-METHYL-19-NORPREGNENE COMPOUNDS
IPC: B04B11/00
Filed: 1970-04-30
Abstract: Novel steroids of the formula (wherein R is H, CHO or C 2-7 alkanoyl R1 is C 1-7 alkyl R11 is O or H (#-OH or #-Oacyl), where acyl is C 2-7 alkanoyl Y is H, Cl or CH 3 X is H 2 or, when ring B is saturated and contains no substituent, =CH 2 and the #6 double bond is optional) are prepared from 3-alkoxy- 13#-alkyl - 17[alpha] - ethyl - 17# - hydroxy - 11#- methylgona - 1,3,5(10) - trienes by known methods. Thus, dehydration to the 17(20)- dehydro compounds, hydroxylation to the 17[alpha],20-diols, Birch reduction to the 2,5(10)- dien-3-enol ethers, hydrolysis to the #4-3-ones and 20-oxidation gives the 17[alpha]-hydroxy-#4-3,20- diones which may then be acylated, either by conventional processes which may necessitate hydrolysis of any #3'5-3-enol acylate formed or directly using as acylating agent the complex formed from a metalloid halide, an organic acid halide and a halogenated aliphatic solvent and conducting the reaction in the presence of a lower nitroparaffin of high dielectric constant and under anhydrous conditions. In another process the 20-hydroxy group of the abovementioned 17[alpha],20-diols is oxidized and the resulting 20-ones are ketalized before Birch reduction, after which they may be hydrolysed directly to product 17[alpha]-hydroxy-#4-3,20-diones or acylated and then hydrolysed to 17[alpha]-acyloxy- #4-3,20-diones. The 16-methylene derivatives are prepared from 3-alkoxy-11#-methyl-19- norpregna - 1,3,5(10),16 - tetraen - 20 - ones by conversion to 16[alpha],17#-pyrazolines, pyrolysis of these to 16-methyl-#16-compounds, peroxidation of these, cleavage of the 16[alpha],17[alpha]-epoxides with strong acids to give 16-methylene-17[alpha]-ols, and then Birch reducing and hydrolysing these and oxidizing the 20-ol products which may then be 17-acylated. 6-Dehydro compounds are prepared by conversion of the #4-3-ones to #3,5-3- enol ethers and then oxidation of these, e.g. with manganese dioxide reagent or dichlorodicyanobenzoquinone while 6[alpha]-methyl derivatives are prepared by subjecting these enol ethers to the Vilsmeier reagent to afford the corresponding 6-iminium intermediates, hydrolysing these to the 6-formyl compounds, reducing these to the 6-hydroxymethyl compounds, hydrolysing and dehydrogenating to the 6- methylene - #4 - 3 - ones, hydrogenating these to the 6#-methyl compounds and epimerizing these alternatively the 6-formyl derivatives may be converted directly to the 6[alpha]-methyl-#4- 3-ones by reduction and acid treatment. The 6 - methyl - #6 - compounds are prepared from the 6-methylene compounds by isomerization. The 6[alpha]-chloro compounds are prepared from the above-mentioned enol ethers by treatment with HOCl or an agent liberating it and epimerization of the 6#-chloro-#4-3-ones thus-produced. The 6 - chloro - #4,6 compounds are prepared (a) by direct dehydrogenation of the 6[alpha]-chloro-#4- compounds or (b) via the 3-enol ethers as described above for the 6-methyl compounds or (c) by converting the 3-keto-#4,6-compounds to 6[alpha],7[alpha]-epoxides, adding on HCl to give the the 6# - chloro - 7[alpha] - hydroxy compounds, and dehydrating these. The 3#-ols are prepared by reduction of the 3-ones they may subsequently be acylated. Starting materials which are racemates may be resolved by standard procedures.