Patent ID: 7214808

Claim:
A process for the production of 4-(17α-substituted-3-oxoestra-4,9-dien-11β-yl)benzaldehyde-(1E or 1Z)-oximes of formula (I), in which R 1 means a hydrogen atom, a C 1-6 -alkyl radical or a C n F 2n+1 radical, R 2 means a C 1-4 -alkyl radical or trifluoromethyl, X means an OH group in E- or Z-position, and Y means an OC 1-6 -alkyl group, an SC 1-6 -alkyl group or an OCH 2 C n F 2n+1 group, whereby n is 1, 2 or 3, characterized in that a 3,3-dimethoxy-5α,10α-epoxy-estr-9(11)-en-17-one of formula (II) in which R 2 has the above-indicated meaning, is converted with an active methylene reagent in an inert solvent into a 5α,10α-epoxy-17(S)-spiroepoxide of formula (IX) in which R 2 has the above-indicated meaning, which, after regio- and stereoselective cleavage of the 17-spiroepoxy group by alkali or alkaline-earth alcoholate, by alkylmercaptans in the presence of alkali hydroxides or potassium-tert-butanolate, by direct cleavage with alkali mercaptides or with perfluoroalkyl alcohols in the presence of alkali in an inert solvent, is opened to a 17α-substituted compound of formula (X) in which R 1 represents a hydrogen atom, Y means an OC 1-6 -alkyl group, an SC 1-6 -alkyl group or an OCH 2 C n F 2n+1 group, whereby n is 1, 2 or 3, and R 2 has the above-indicated meaning, which optionally is converted by reaction of the 17β-hydroxyl group with alkyl halides or haloalkyl fluorides in the presence of strong bases in an inert solvent into the 17β-ethers or 17β-fluoroalkyl ethers of formula (X), in which R 1 is a C 1-6 -alkyl radical or a C n F 2n+1 radical, whereby n is 1, 2 or 3, and R 2 and Y have the above-indicated meanings, which is reacted with a 4-bromobenzaldehyde ketal, magnesium and Cu(I)Cl at temperatures of between −35° C. and room temperature to form the corresponding 3,3-dimethoxy-5α-hydroxy-17α-CH 2 Y-11β-benzaldehyde ketal of formula (XI) in which R 1 is a hydrogen atom, a C 1-6 alkyl radical or a C n F 2n+1 radical, whereby n is 1, 2 or 3, R 2 and Y have the above-indicated meanings, and R 3 stands for a methyl radical or an ethylidene group, which is converted by acid hydrolysis of the protective groups into an 11β-benzaldehyde derivative of formula (XII), in which R 1 , R 2 and Y have the above-indicated meanings, and the aldehyde function is converted selectively by hydroxylammonium salts into a mixture of E/Z-benzaldoximes of formula (I), in which X means an OH group in E- or Z-position.