Patent ID: 7268241
Filing Date: 2007-09-11
Classification: C07J,Y02P

Abstract:
1. A process for preparing a 4-(17α-methyl-substituted 3-oxoestra-4,9-dien-11β-yl) benzaldehyde-(1E or 1Z)-oxime of formula (I) in which R R X is an OH group in E- or Z-position, Y is an OC n is 1, 2 or 3, comprising converting a 3,3-dimethoxy-estra-5(10),9(11)-en-17-one compound of formula (IX) in which R with an active methylene reagent in an inert solvent into a spiroepoxide compound of formula (X) in which R cleaving the 17-spiroepoxy group of the compound of formula (X) with an alkali or alkaline-earth alcoholate, alkali or alkaline-earth thiol alcoholate or a trifluoroalkyl alcohol and potassium-tert-butanolate in an inert solvent, and forming a 17α-CH in which R R Y is an OC optionally reacting the 17β-hydroxyl group of the compound of formula (XI) with an alkyl halide or fluoroalkyl iodide in the presence of a strong base in an inert solvent to form a 17β-ether of formula (XI″), in which R R Y is an OC epoxidizing the compound of formula (XI) or (XI″) on the 5(10)-double bond thereof, producing a mixture of 5α, 10α-epoxy- and 5β, 10β-epoxy-17α-methyl-substituted estr-9(11)-ene-3,3-dimethyl ketals of formula (XII) in which R R Y is an OC reacting the compound of formula (XII) with a 4-bromobenzaldehyde ketal, magnesium and Cu(I)Cl at a temperature of between −35°C. and room temperature form a 3,3-dimethoxy-5α-hydroxy-17α-methyl-substituted 11α,β-benzaldehydedimethyl ketal of formula (XIII) in which R R Y is an OC subjecting the compound of formula (XIII) to acid hydrolysis to cleave any protective groups, to form a mixture of 11α,β-benzaldehyde compounds of formula (XIV) in which R R Y is an OC isolating by crystallizing a pure 11β-benzaldehyde compound, and converting the aldehyde function of said 11β-benzaldehyde compound by a hydroxylammonium salt in the presence of a base at room temperature into a mixture of E/Z-benzaldoximes of formula (I).