Verfahen zur Herstellung von neuen in 9α-Stellung unsubstituierten 6,11β-Dichlor-19-norsteroid-4-en (bzw. 4,6-dien)-3-onen

摘要

1,202,521. 9α- Unsubstituted - 11# - chloro - 19 - nor - steroids. GLAXO LABORATORIES Ltd. 8 Aug., 1967 [29 July, 1966; 18 May, 1967], Nos. 34275/66 and 23066/67. Heading C2U. [Also in Division A5] Novel 9α- unsubstituted 11# - chloro - 19 - nor-steroids are prepared (1) by reaction of the corresponding 11α-ols with a reagent of the formula (in which R1 and R2 are each C 1-8 alkyl, aralkyl or aryl, or NR1R2 is a heterocycle which may contain further hetero atoms, R3 is Cl or F, R4 is Cl or F and R5 is H or R4 and R5 together represent a carbon-carbon bond, R6 is Cl or F and R7 is Cl, F or CF 3 ) the reaction being effected in the presence of chloride ions when neither nor R4 is Cl, other reactive OH groups preferably being protected; or (2) by reaction of the corresponding 11α- alkyl or aryl - sulphonyloxy compounds with a source of chloride ions; or (3) by reaction of the 11α-ols with a triaryl - phosphine or - phosphite and chlorine or a chloroalkane. In the products 3- and 17- keto groups may be reduced, 3- and 17-hydroxy groups may be acylated or etherified or the corresponding keto groups may be enolacylated or -etherified, a 17-keto group may be reacted with an aliphatic or araliphatic organometallic compound to introduce an aliphatic or araliphatic group and form the 17-ol, a 3-acyloxy or -alkoxy steroid 3,5-diene may be chlorinated to give a 6# - chloro - 3 - oxo - #4 - steroid and this may be epimerized by enol acylation or alkylation followed by hydrolysis, a #3'5 - 3 - enol acylate or ether may be converted into the #4'6 - 3 - ketone e.g. with chloranil or manganese dioxide, and a 3,17α- diacyloxy - #3'5 - steroid may be selectively hydrolysed to the 17α- acyloxy - #4 - 3 - keto - steroid. Other standard processes are also referred to. 11α,17α- Dihydroxy - 19 - norpregn - 4 - ene - 3,20 - dione is prepared from 21 - iodo - pregna - 1,4 - diene - 11#,17α- diol - 3,20 - dione by conversion to the 21 - unsubstituted compound, then to the #9(11) - compound, then to 3,17α- dihydroxy - 19 - norpregna - 1,3,5(10),9(11) - tetraen - 20 - one, then to the 3 - alkoxy compound, then to the 20 - ketal, hydroboration to the 11α- ol and Birch reduction and hydrolysis to the required product. 11α- Hydroxy - estra - 4,6 - diene - 3,17 - dione is prepared by the action of chloranil on 3- ethoxy - 11α- hydroxyestra - 3,5 - dien - 17 - one, prepared by enol etherification of the #4-3-one. 11α- Hydroxy - 19 - nor - pregn - 4 - ene - 3,20 - dione, is prepared by Birch reduction and hydrolysis of 20,20 - ethylenedioxy - 3 - methoxy - 19 - nor - pregna - 1,3,5(10) - trien - 11α- ol. 11α- Mesyloxyestr - 4 - ene - 3,11 - dione is prepared from the 11α-ol.