Patent ID: 6603031
Filing Date: 2003-08-05
Classification: A61P,B21C,C07C,C07D,Y02P

Abstract:
A process for the production of a compounds of formula IIa in whichE is a side chain, E is a side chain, R7, R8, are each, independently of one another, a hydrogen atom or a methyl group, or together are an exocyclic methylene group or a cyclopropyl ring, Y2 is a hydrogen atom or a group â€”(CO)R5, Y3 is a hydrogen atom, a hydroxy group, a halogen atom, a group â€”O(CO)R5 or an OR5 group, R5 is an aromatic radical with 5 to 12 C atoms or an aliphatic C1-C12 alkyl radical, which optionally is interrupted by 1-2 oxygen atoms, 1-2 sulfur atoms and/or 1-2 NH groups and/or optionally is substituted by 1-2 hydroxy groups, 1-2 amino groups, 1-2 SH groups, 1-2 COOH groups and/or 1-2 phenyl groups, Y5 is a fluorine atom, a (CH2)nâ€”OH group or a (CH2)nâ€”O(CO)R5 group, n is 0 to 4, and optionally present hydroxy groups are each indpendently optionally present in protected form, said process comprising:converting a ketone of general formula XIIIc â€ƒin which E is a side chain, and optionally present keto groups and/or hydroxy groups are present in protected form, by reaction with trimethylsilylacetic ester in the presence of a base or with a Wittig reagent in an aprotic solvent into a compound of formula XXXIVc â€ƒin which Y6 is C1-C6 alkyl group, a benzyl group, or a phenyl group; converting the ester group by reaction with a reducing agent in hexane, toluene, tetrahydrofuran, diethyl ether or dioxane to form an allyl alcohol of formula XXXVc converting the allyl alcohol into a compound of formula XXXVc â€ƒin which L is a leaving group, which is isolated or optionally produced in situ and immediatelly further reacted to form a Wittig reagent of formula XXXVIc, â€ƒin which G is a C1-C10 alkyl group, a C1-C10 alkoxy group, a phenyl radical or a phenoxy radical; reacting the compound of formula XXXVIc with a ketone of formula XXXIIIc â€ƒin which Yâ€²3 is a hydrogen atom, a halogen atom, a protected hydroxy group, a group â€”O(CO)R5 or an OR5 group; and optionally cleaving protective groups.