Synthesis of 18,18-difluoro- or 18,18,18-trifluoro-3-methoxy-12- oxaestra-1,3,5(10)-trienes

Article abstract of DOI:10.1016/S0040-4020(98)00599-7

Titanium tetrachloride mediated dialkylation of acetic anhydride, trifluoroacetic anhydride or difluorochloroacetic anhydride by 1,8- bis(trimethylsilyl)-2,6-octadiene (BISTRO) leads, respectively, to dl- 1- methyl-2,5-divinylcyclopentan-1-ol dl-1-difluoromethyl-2,5- divinylcyclopentan-1-ol or dl-1-trifluoromethyl-2,5-divinylcyclopentan-1-ol. Esterification of these compounds with 4-methoxybenzocyclobutene-l-carboxylic acid and then pyrolysis led to 3-methoxy-12-oxa-17-vinylestra-1,3,5(10)- trien-11-one and to corresponding 18,18-difluoro or 18,18,18-trifluoro derivatives. Further transformations give rise to 3-methoxy- 12-oxa-17-(2- oxoethyl)- 18.18-difluoroestra-1,3,5(10)-trien-11-one and to the corresponding 18,18,18-trifluoro derivative.