GB497022A - Manufacture of derivatives of cyclopentano-polyhydrophenanthrene - Google Patents

Abstract

Unsaturated derivatives of the cyclopentanopolyhydro-phenanthrene are prepared by replacing, by the Curtius or Hoffmann degradation, the carboxyl group in a saturated acid of the general formula <FORM:0497022/IV/1> where R stands for a -COOH or a <FORM:0497022/IV/2> group, by the amino group, oxidizing the 3-hydroxyl group to the keto group during or after the degradation process, and subsequently treating with a halogenating agent, converting the amine into the corresponding alcohol or ketone, and splitting off hydrogen halide either directly after the halogenation or at any subsequent stage in the process. In examples: (1) acetyl-bisnorlithocholic acid is converted into its acid chloride by thionyl chloride and then degraded by the process described in Specification 465,960 through the azide and isocyanate to the corresponding amine. A glacial acetic acid solution of this amine is then oxidized by chromic oxide to 3-oxo-ternorcholanyl amine, brominated, and hydrogen bromide withdrawn with silver acetate. The unsaturated oxo-amine is then further treated according to the process described in Specification 465,960 to give progesterone. If the brominated oxo-amine above is treated under reflux with alcoholic alkali, there is obtained 3-oxo-4-hydroxy-ternorcholanylamine; (2) 3-acetoxyaetiocholanyl carboxylic acid-(19) is transformed via the corresponding chloride into the amine as described in Specification 492,729. The amine acetate is then oxidized in glacial acetic acid solution with chromic oxide to 3-oxo-aetiocholanylamine which is brominated and then treated with sodium nitrite and acetic acid. Debromination of the product with silver acetate in glacial acetic acid yields the acyl-testosterone. Specification 481,028 also is referred to.