Patent GB-956804-A (GB)
Title: Steroids
IPC: C07J71/00
Filed: 1960-11-29
Abstract: The invention comprises steroids of the general formula: <FORM:0956804/C2/1> wherein R represents an alpha- or beta-fluorine or chlorine atom, P and Q each represent a hydrogen atom or a lower alkyl, halogenated lower alkyl, monocyclic cycloalkyl, monocyclic aryl, monocyclic aryl lower alkyl, monocyclic heterocyclic, or monocyclic heterocyclic lower alkyl group, or P and Q together with the carbon atom to which they are joined represent a cycloalkyl or a saturated monocyclic heterocyclic group, and the preparation thereof in the case where R is in the beta configuration by dehydrating 5a -hydroxy-steroids of the general formula: <FORM:0956804/C2/2> wherein R, P and Q have the above significance, for example, with a dilute base such as sodium hydroxide or carbonate, or with an acid chloride such as sulphonyl chloride or phosphorus oxychloride, and, when required, inverting the group R to form the corresponding compounds of the first general formula above wherein R is in the alpha-configuration, for example, with hydrogen chloride.  This process may be modified in that the 5a -hydroxy-steroids of the second general formula above are prepared by reacting steroids of the general formula: <FORM:0956804/C2/3> with a per-acid such as perbenzoic, monoperphthalic or peracetic acid, to form 5a , 6a -epoxy-steroids of the general formula: <FORM:0956804/C2/4> treating the 5a , 6a -epoxy-steroids with boron trifluoride or boron trichloride to form 6b -halo-5a -hydroxy-steroids of the general formula: <FORM:0956804/C2/5> wherein R represents a fluorine or chlorine atom, and treating the compounds of the previous general formula either with an acid-preferably a mineral acid, to form steroids of the general formula: <FORM:0956804/C2/6> wherein R has the above significance, and acetalizing or ketalizing as required, or with a lower alkanol to form steroids of the general formula: <FORM:0956804/C2/7> wherein R has the above significance, hydrolyzing these steroids with a strong acid and acetalizing or ketalizing as required (if the hydrolysis step is carried out in the presence of an aldehyde or ketone the subsequent step of acetalizing or ketalizing is not required).  The invention also includes a process for the preparation of steroids of the general formula: <FORM:0956804/C2/8> wherein P and Q have the above significance, by chlorinating steroids of the general formula: <FORM:0956804/C2/9> with an N-chloramide or N-chlorimide to form the 6b -chloro compound and, if required, isomerizing to the 6a -chloro compound for example, with hydrogen chloride in glacial acetic acid, the steroids of the last general formula may be prepared by treating steroids of the general formula: <FORM:0956804/C2/100> wherein P and Q have the above significance, with a lower alkyl formate, and the steroids of the last general formula may be prepared by reacting 16a , 17a -dihydroxy-progesterone with an aldehyde or ketone of the formula <FORM:0956804/C2/111> wherein P and Q have the above significance. The term "lower" appended to a radical is meant to indicate that the radical has less than 8 carbon atoms.  Therapeutic compositions having progestational activity and which may be used perorally or parenterally contain as the active ingredients steroids of the first general formula above.