Patent GB-851998-A (GB)
Title: New cyclopentanophenanthrene derivatives and processes for the production thereof
IPC: C07J5/00
Filed: 1957-01-21
Abstract: The invention comprises 4-alkyl or aralkyl pregnane derivatives of the general formula; <FORM:0851998/IV(b)/1> in which R is an alkyl or aralkyl group, R1 is a b -hydroxy or a keto group, and R2 is hydrogen or an acyl group; also a process for their preparation by partially hydrolysing a 3,20-bisethylene ketal of pregnane-11b ,17a ,21-triol-3,20-dione or of pregnane-17a ,21-diol-3,11,20-trione with acetic acid to form the corresponding 20-monoethylene ketal, reacting the 20-ethylene ketal with ethyl formate in the presence of sodium hydride, treating the resulting 4-hydroxymethylene derivative with an alkyl or aralkyl iodide to form the corresponding 4-alkyl or aralkyl 4-formyl derivative, eliminating carbon monoxide by treatment with a mild base and hydrolysing the 20-ketal group or alternatively eliminating carbon monoxide and hydrolysing in a single step with a mineral acid to form a 4-alkyl or aralkyl pregnane-11b ,17a ,21-triol-3,20-dione or pregnane-17a , 21-diol-3,11,20-trione, treating one of the last-mentioned compounds with an esterifying agent, e.g. an acid anhydride or acid halide to form the 21-ester thereof, brominating to form the corresponding 4-bromo derivative, dehydrobrominating with a tertiary base and saponifying the ester group.  In examples (1) the 3,20-diethylene ketal of pregnane-17a , 21-diol-3, 11,21-trione is hydrolysed with 90% acetic acid to the 20-monoethylene ketal, which is stirred in benzene with ethyl formate and sodium hydride under nitrogen, the resulting 4-hydroxy-methylene derivative suspended in benzene with sodium hydride and treated with methyl iodide, giving the 4-methyl-4-formyl derivative, which is passed through a column of alkaline activated alumina and the resulting 20-ethylene ketal of 4a -methyldihydrocortisone hydrolysed in aqueous methanolic sulphuric acid and then acylated to the 21-acetate, propionate, cyclopentylpropionate and benzoate of 4a -methyl-dihydrocortisone; (2) the 4-methyl-4-formyl intermediate of (1) is refluxed with aqueous methanolic sulphuric acid giving 4a -methyldihydrocortisone; (3) to (5) as in (1) but using the appropriate iodide to yield 4a -ethyl-, 4a -propyl-, and 4a -benzyl-dihydrocortisone and its 21-esters; (6) the 3,20-diethylene ketal of pregnane-17a ,21-diol-3,11,20-trione is reduced with lithium aluminium hydride to the 11b -hydroxy derivative, which is then treated as in (1) to give 4a -methyl-pregnane 11b ,17a ,21-triol-3,20-dione and its esters and similarly the corresponding 4a -ethyl-, propyland benzyl-compounds; (7) a 21-ester of 4a -methyl-dihydrocortisone prepared as in (1) is brominated in acetic acid containing HBr, the resulting 4-methyl-4-bromo compound refluxed with collidine to give the corresponding 21-ester of 4-methyl-D 4-pregnene-17a ,21-diol-3,11,20-trione and then saponified to the free alcohol; (8) to (14) similarly are prepared the corresponding 4-ethyl-, 4-propyl- and 4-benzyl derivatives and also the 4-methyl-, ethyl-, propyl- and benzyl derivatives of D 4-pregnene- 11b ,17a , 21-triol-3,20-dione.