GB875549A - Process for the preparation of 19-nor-steroid compounds - Google Patents

Abstract

D 4-19-Nor-steroids unsubstituted in the 3-position are prepared by reacting a D 4-3-keto-19-nor-steroid with a hydrocarbon thiol or a hydrocarbon dithiol to form the corresponding 3-thioketal and then reacting this with an alkali metal in the presence of liquid ammonia. The thioketalization may be effected, for example, in the presence of zinc chloride or hydrochloric acid and a dehydrating agent, such as sodium sulphate, or in the presence of p - toluene - sulphonic acid and a water-immiscible organic solvent, or in the presence of glacial acetic acid and a Lewis acid such as boron trifluoride or the etherate thereof. Preferably, a hydrocarbon dithiol such as ethane, propane or butane dithiol is used, to give a cyclic thioketal, but monothiols such as ethyl, propyl, benzyl or phenyl thiol may also be used, to give a non-cyclic thioketal. During the reaction with liquid ammonia, reducible keto groups e.g. in the 20-position, are converted to hydroxyl groups, which may then be reconverted to keto groups by oxidation with, for example, chromium trioxide and sulphuric acid, 21-hydroxyl groups, if present, being protected prior to the oxidation, by esterification and then liberated again by saponification after the oxidation. Examples illustrate the preparation of various D 4-19-nor-androstenes and pregnenes containing in the 17-position a - and b -hydroxy, keto, and a -alkyl and alkenyl groups, in the 20-position keto groups, in the 21-position hydrogen or hydroxyl groups and in the 11-position hydrogen, b -hydroxy or keto groups. Specifications 811,961 and 847,713 are referred to.