SYNTHESIS OF 8-DIFLUORO-3-METHOXY-12-OXAESTRA-1,3,5(10)-TRIENES OR -TRIFLUORO-3-METHOXY-12-OXAESTRA-1,3,5(10)-TRIENES

Titanium tetrachloride mediated dialkylation of acetic anhydride, trif luoroacetic anhydride or difluorochloroacetic anhydride by 1,8-bis(tri methylsilyl)-2,6-octadiene (BISTRO) leads. respectively, to dl-1-methy l-2,5-divinylcyclopentan-1-ol. dl-1-difluoromethyl-2,5-divinylcyclopen tan-1-ol or dl-1-trifluoromethyl-2,5-divinylcyclopentan-1-ol. Esterifi cation of these compounds with 4-methoxybenzocyclobutene-1-carboxylic acid and then pyrolysis led to ethoxy-12-oxa-17-vinylestra-1,3,5(10)-t rien-11-one and to corresponding 18,18-difluoro or 18,18,18-trifluoro derivatives. Further transformations give rise to 3-methoxy- oethyl)-1 8,18-difluoroestra-1,3,5(10)-trien-11-one and to the corresponding 18, 18,18-trifluoro derivative. (C) 1998 Elsevier Science Ltd. All rights reserved.