Method for preparing oestrogen derivatives

A process for the preparation of compounds of formula (I)

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• in which
• either R1 and R2, identical or different, represent a benzyl group or a linear, branched or cyclic alkyl, alkenyl or alkynyl radical containing from 1 to 8 carbon atoms
• or R1 and R2 form together with the nitrogen atom which carries them an aromatic or non-aromatic, saturated or unsaturated heterocycle with 5 to 6 members, optionally containing from 1 to 3 additional heteroatoms, and optionally connected to another ring,
• R3 represents a hydrogen atom or a protective group of the hydroxy function,
• n is an integer from 2 to 8,
• characterized in that a compound of formula (II)
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• K representing a protected ketone function in particular in the form of ketal, thioketal or mixed ketal, is treated
• with a silylation agent in the presence of a base, in order to obtain the silylated enol of formula (III)
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• in which Ra, Rb and Rc, identical or different, represent an alkyl radical containing from 1 to 4 carbon atoms or a phenyl radical,
• which is reacted with
• an organocuprate derivative, derived from the organometallics R5MgHal or R5Li, Hal being a halogen atom and generated in a catalytic or stoichiometric fashion, in which R5 represents the
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• group,
• n, R1 and R2 being as defined above, the bond being made at the level of the phenyl,
• in order to obtain a compound of formula (III′) which is isolated or non-isolated:
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• then a deprotection agent in order to obtain a compound of formula (IV):
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• which is treated with an aromatization agent in order to obtain the expected compound of formula (I) which ,if appropriate, is subsequently deprotected in order to obtain a compound of formula (I) with R3 representing a hydrogen atom.