RU 58668 can be prepared according to the multistep synthesis described in Scheme 20326301a. It starts with the copper(I) catalyzed regiospecific addition of the Grignard reagent derived from 4-bromophenol, protected as its trimethylsilyl ether, on the 5alpha,10alpha-epoxyestr-9(11)-ene-3,17-dione 3-(1,2-ethanediyl) cyclic acetal (I). The acidic treatment of the crude 11beta-aryl-5alpha-hydroxyestr-9-ene-3,17-dione cyclic acetal thus produced yielded the 11beta-(4-hydroxyphenyl)estradienedione (II), by simultaneous desilylation, deketalization of the 3-keto group and dehydration. Alkylation of the phenolic hydroxyl group was performed using 1-bromo-5-chloropentane, with aqueous sodium hydroxide in acetone yielding (III). The A-ring of the chloropentyl ether (III), was aromatized by treatment with a mixture of acetyl bromide and acetic anhydride in dichloromethane. The phenolic acetate obtained was immediately submitted to saponification followed by reduction of the 17-keto group with sodium borohydride, leading to the formation of the crystalline chlorinated estradiol derivative (IV). Halogen exchange with sodium iodide gave rise to the formation of the iodo derivative (V). The sulfur atom was introduced by substitution with potassium thioacetate, to produce the thioester (VI). Saponification of the acetate generated the sodium thiolate, which was immediately alkylated with 5-iodo-1,1,1,2,2-pentafluoropentane (obtained through the iodination of the corresponding pentafluoropentanol), yielding the sulfide (VII). Oxidation of the latter compound followed by chromatography and recrystallization afforded pure RU 58668.

RU 58668 can be prepared according to the multistep synthesis described in Scheme 20326301a. It starts with the copper(I) catalyzed regiospecific addition of the Grignard reagent derived from 4-bromophenol, protected as its trimethylsilyl ether, on the 5alpha,10alpha-epoxyestr-9(11)-ene-3,17-dione 3-(1,2-ethanediyl) cyclic acetal (I). The acidic treatment of the crude 11beta-aryl-5alpha-hydroxyestr-9-ene-3,17-dione cyclic acetal thus produced yielded the 11beta-(4-hydroxyphenyl)estradienedione (II), by simultaneous desilylation, deketalization of the 3-keto group and dehydration. Alkylation of the phenolic hydroxyl group was performed using 1-bromo-5-chloropentane, with aqueous sodium hydroxide in acetone yielding (III). The A-ring of the chloropentyl ether (III), was aromatized by treatment with a mixture of acetyl bromide and acetic anhydride in dichloromethane. The phenolic acetate obtained was immediately submitted to saponification followed by reduction of the 17-keto group with sodium borohydride, leading to the formation of the crystalline chlorinated estradiol derivative (IV). Halogen exchange with sodium iodide gave rise to the formation of the iodo derivative (V). The sulfur atom was introduced by substitution with potassium thioacetate, to produce the thioester (VI). Saponification of the acetate generated the sodium thiolate, which was immediately alkylated with 5-iodo-1,1,1,2,2-pentafluoropentane (obtained through the iodination of the corresponding pentafluoropentanol), yielding the sulfide (VII). Oxidation of the latter compound followed by chromatography and recrystallization afforded pure RU 58668.

RU 58668 can be prepared according to the multistep synthesis described in Scheme 20326301a. It starts with the copper(I) catalyzed regiospecific addition of the Grignard reagent derived from 4-bromophenol, protected as its trimethylsilyl ether, on the 5alpha,10alpha-epoxyestr-9(11)-ene-3,17-dione 3-(1,2-ethanediyl) cyclic acetal (I). The acidic treatment of the crude 11beta-aryl-5alpha-hydroxyestr-9-ene-3,17-dione cyclic acetal thus produced yielded the 11beta-(4-hydroxyphenyl)estradienedione (II), by simultaneous desilylation, deketalization of the 3-keto group and dehydration. Alkylation of the phenolic hydroxyl group was performed using 1-bromo-5-chloropentane, with aqueous sodium hydroxide in acetone yielding (III). The A-ring of the chloropentyl ether (III), was aromatized by treatment with a mixture of acetyl bromide and acetic anhydride in dichloromethane. The phenolic acetate obtained was immediately submitted to saponification followed by reduction of the 17-keto group with sodium borohydride, leading to the formation of the crystalline chlorinated estradiol derivative (IV). Halogen exchange with sodium iodide gave rise to the formation of the iodo derivative (V). The sulfur atom was introduced by substitution with potassium thioacetate, to produce the thioester (VI). Saponification of the acetate generated the sodium thiolate, which was immediately alkylated with 5-iodo-1,1,1,2,2-pentafluoropentane (obtained through the iodination of the corresponding pentafluoropentanol), yielding the sulfide (VII). Oxidation of the latter compound followed by chromatography and recrystallization afforded pure RU 58668.

RU 58668 can be prepared according to the multistep synthesis described in Scheme 20326301a. It starts with the copper(I) catalyzed regiospecific addition of the Grignard reagent derived from 4-bromophenol, protected as its trimethylsilyl ether, on the 5alpha,10alpha-epoxyestr-9(11)-ene-3,17-dione 3-(1,2-ethanediyl) cyclic acetal (I). The acidic treatment of the crude 11beta-aryl-5alpha-hydroxyestr-9-ene-3,17-dione cyclic acetal thus produced yielded the 11beta-(4-hydroxyphenyl)estradienedione (II), by simultaneous desilylation, deketalization of the 3-keto group and dehydration. Alkylation of the phenolic hydroxyl group was performed using 1-bromo-5-chloropentane, with aqueous sodium hydroxide in acetone yielding (III). The A-ring of the chloropentyl ether (III), was aromatized by treatment with a mixture of acetyl bromide and acetic anhydride in dichloromethane. The phenolic acetate obtained was immediately submitted to saponification followed by reduction of the 17-keto group with sodium borohydride, leading to the formation of the crystalline chlorinated estradiol derivative (IV). Halogen exchange with sodium iodide gave rise to the formation of the iodo derivative (V). The sulfur atom was introduced by substitution with potassium thioacetate, to produce the thioester (VI). Saponification of the acetate generated the sodium thiolate, which was immediately alkylated with 5-iodo-1,1,1,2,2-pentafluoropentane (obtained through the iodination of the corresponding pentafluoropentanol), yielding the sulfide (VII). Oxidation of the latter compound followed by chromatography and recrystallization afforded pure RU 58668.