Patent GB-761351-A (GB)
Title: Cyclopentanophenanthrene derivatives and a method for the preparation thereof
IPC: C07J5/00
Filed: 1953-03-05
Abstract: The invention comprises D 1-allopregnene-11a ,17a ,21 - triol - 3,20 - dione, D 1,4 - pregnadiene - 11a , 17a ,21 - triol - 3,20 - dione, their 11,21- and 21-esters, their preparation from the corresponding allopregnane-11a ,17a ,21-triol-3, 20-diones by mono- or dibromination, followed by dehydrobromination of the 2-bromo- or 2,4-dibromo-derivatives so obtained, and also a process for the preparation of D 4-pregnene11a ,17a ,21-triol-3,20-dione and its 21- and 11,21-esters (a) from allopregnane-11a ,17a ,21-triol 11,21- or 21-esters by dibromination and treattreatment of the 2,4-dibromo-compound with sodium iodide in the presence of a lower aliphatic ketone to form the corresponding 2-iodo-D 4-pregnene, which is then deiodinated with e.g. chromous chloride, sodium bisulphite, collidine, dimethyl aniline, or Raney nickel; (b) from 16a ,17a  - oxido - allopregnane - 11a ,21-diol-3,20-dione or an 11,21- or 21-ester thereof by bromination in the presence of HBr, thereafter treating the resultant 2,4,16-tribromoallopregnane - 11a ,17a ,21 - triol - 3,20 - dione compound with sodium iodide, and finally dehalogenating the 2-iodo-16-bromo-D 4-pregnene produced.  The D 4-pregnene-11a ,17a ,21-triol-3,20-dione 21-esters obtained by method (a) can be further oxidized to yield 21-esters of cortisone.  In examples: (1) allopregnane-11a ,17a ,21-triol - 3,20 - dione 11,21 - diacetate is brominated in glacial acetic acid containing HBr, and the resultant 2-bromo-allopregnane-11a ,17a ,21-triol - 3,20 - dione diacetate refluxed with g -collidine or 2,6-lutidine to yield D 1-allopregnen-11a ,17a ,21 - triol - 3,20 - dione 11,21 - diacetate, which is saponified to the free triol and reacetylated to the 21-mono-acetate, alternatively the 2-bromo-intermediate is dehydrohalogenated by treatment with 2,4-dinitrophenylhydrazine or semicarbazide hydrochloride and sodium acetate, and the resultant hydrazone cleaved with hydrohalic or pyruvic acid; (2) allopregnane - 11a ,17a ,21 - triol - 3,20 - dione 11,21 - diacetate is brominated, giving the 2,4-dibromoderivative, which is then refluxed with collidine to yield D 1,4 - pregnadiene - 11a ,17a ,21 - triol-3,20 - dione 11,21 - diacetate, which is saponified and reacetylated to the 21-acetate; (3) the 2,4-dibromo derivative from (2) is treated with sodium iodide in acetone, giving 2-iodo-D 4-pregnene - 11a ,17a ,21 - triol - 3,20 - dione 11,21-diacetate, which is reduced with chromous chloride to D 4 - pregnene - 11a ,17a ,21 - triol-3,20-dione 11,21-diacetate, saponified to the free triol and reacetylated to the 21-acetate, which s then oxidized with chromic acid to cortisone 21-acetate; (4) 16a ,17a  - oxido - allopregnane-11a ,21 - diol - 3,20 - dione 11,21 - diacetate is brominated in acetic acid containing HBr to yield 2,4,16 - tribromo - allopregnane - 11a ,17a , 21 - triol - 3,20 - dione diacetate, which with NaI in acetone gives 2-iodo-16-bromo-D 4-pregnene - 11a ,17a ,21 - triol - 3,20 - dione 11,21-diacetate which on refluxing with Raney nickel in ethanol gives D 4-pregnene-11a ,17a ,21-triol-3,20 - dione diacetate; (5) allopregnane - 11a , 17a ,21 - triol - 3,20 - dione 21 - monoacetate is brominated in chloroform-acetic acid, the 2,4-dibromo-product treated with sodium iodide in acetone and the 2-iodo-D 4-pregnene obtained reduced with aqueous sodium bisulphite to D 4 - pregnene - 11a ,17a ,21 - triol - 3,20 - dione 21-monoacetate, which is oxidized to cortisone 21-acetate as in (3).  Specifications 693,991 and 748,887 are referred to.