GB792727A - Improvements in or relating to cyclopentanophenanthrene compounds and the preparation thereof - Google Patents

Abstract

The invention comprises 4-chloro-3-oxo-D 4-cyclopentanophenanthrenes of the androstane and pregnane series having apart from the substituent in the 17-position the general formula: <FORM:0792727/IV (b)/1> wherein R represents: <FORM:0792727/IV (b)/2> and the preparation thereof by chlorinating the required 3-oxo-D 4-cyclopentanophenanthrene of the androstane and pregnane series and treating the resulting 4 : 5-chloride with a base to remove the elements of hydrogen chloride. The chlorination may be effected in an organic solvent with approximately one molar equivalent of chlorine (preferably also dissolved in an organic solvent) at a temperature not in excess of 40 DEG C., a temperature between - 35 DEG C. and + 5 DEG C. being particularly suitable. The chlorination is preferably effected in the absence of light. Suitable organic solvents are dioxan, ether, carbon tetrachloride and a lower aliphatic acid. The base used to remove the elements of hydrogen chloride may be a tertiary base such as collidine, lutidine or pyridine. The removal of the elements of hydrogen chloride may also be carried out by percolating a solution of the 4 : 5-dichloride, e.g. in benzene, through a column of alumina. Suitable reactants for the above process are androst-4-ene-3,17-dione, methyltestosterone and esters thereof, testosterone and esters thereof, 17-chloroandrost-4-en-3-one, progesterone, pregn-4-ene-3,20-diones containing an oxo, hydroxy or acyloxy group at C11, e.g. 11a -hydroxy-progesterone, pregn-4-ene-3,20-diones containing a hydroxy or acyloxy group at C17 and/or C21, and pregn-4-ene-3,20-diones containing hydroxy or acyloxy groups at C17 and C21 and an oxo, hydroxy or acyloxy group at C11, e.g. cortisone acetate. The esters of testosterone may be derived from acids containing not more than 12 carbon atoms, e.g. the ester may be the propionate, trimethylacetate, valerionate, heptylate, undecylenate, cyclopentylpropionate, cyclohexylpropionate, phenylacetate, phenylbutyrate or hexahydrobenzoate of testosterone. In the examples the following 4-chloro-3-oxo-D 4-cyclopentanophenanth rene compounds are prepared, the corresponding 4,5-dichloro-cyclopentanophenanthrene intermediate being indicated in each case in brackets: 4-chlorotestosterone propionate (4,5 - dichloro - 17b -propionoxyandrostan - 3 - one), 4 - chlorotestosterone (4,5 - dichloro - 18b - hydroxyandrostan - 3 - one), 4 - chloro - methyltestosterone (4,5 - dichloro - 17b - hydroxy - 17a -methylandrostan - 3 - one), 4 - chloro - androst4 - ene - 3,17 - dione (4,5 - dichloro - androstene3,17 - dione), 4 - chlorocortisone acetate (21-acetoxy - 4,5 - dichloro - 17a - hydroxypregnane - 3,11,20 - trione), 4 - chloro - 11a -hydroxyprogesterone (4,5 - dichloro - 11a -hydroxypregnane - 3,20 - dione), 4 - chloroprogesterone (4,5 - dichloropregnane - 3,20-dione), and 21 - acetoxy - 4 - chloro - pregn - 4-ene - 3,20 - dione (4,4 - dichloro - pregnane-3, 20-dione.