Process for preparing (15alpha,16alpha,17beta)-estra-1,3,5(10)-triene- 3,15,16,17-tetrol (estetrol) and intermediates of said process

Process for the synthesis of Estetrol, (15α,16α,17β)-estra-1,3,5(10)-triene-3, 15,16,17-tetrol, comprising the following steps:

• A) oxidation of compound (17β)-3-(phenylmethoxy)-estra-1,3,5(10),15-tetraen-17-ol (intermediate 1) to give the compound (17β)-3-(phenylmethoxy)-estra-1,3,5(10)-triene-15, 16,17-triol (intermediate 2):
• wherein Bn=benzyl, and in which the configuration of the carbon atoms 15 and 16 of the steroidal skeleton is not fixed;
• B) acetylation of intermediate 2 to give compound (15α,16α,17β)-3-(phenylmethoxy)-estra-1, 3,5(10)-triene-15,16,17-triol triacetate (intermediate 3) passing through intermediate 3′ in which the configuration of the carbon atoms 15 and 16 of the steroidal skeleton is not fixed:
• C) transformation of intermediate 3, passing through the compound (15α,16α,17β)-3-hydroxy-estra-1, 3,5(10)-triene-15,16,17-triol triacetate (intermediate 4), which is preferably not isolated, into Estetrol:
• D) purification of Estetrol obtained in step C).