9,10-Seco-steroid preparation
AssigneeHoffmann-La Roche Inc.
InventorsJean-Marie Cassal, Andor Furst, Werner Meier
Life of this patent
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Abstract
A process for the preparation of 9,10-seco-steroids of the formula ##STR1## wherein R.sup.1 and R.sup.2 independently are hydrogen, amino, OR.sup.5, OCOR.sup.6 or NHCOR.sup.5 wherein R.sup.5 is hydrogen or lower alkyl and R.sup.6 is lower alkyl or phenyl; R.sup.3 is lower alkyl; R.sup.4 is oxo, ##STR2## wherein R.sup.13 is lower alkyl, lower alkoxy - lower alkylene, tetrahydropyranyl or tetrahydrofuryl, R.sup.14 is lower alkyl or aryl and R.sup.15 and R.sup.16 are lower alkyl or taken together form lower alkylene or arylene, and n is 1 or 2 is disclosed. The 9,10-seco-steroids of this invention are useful intermediates for the preparation of steroids.
Claims8
A process for the preparation of a compound of the formula ##STR14## wherein R.sup.1 and R.sup.2 independently are hydrogen, amino, OR.sup.5, OCOR.sup.6 or NHCOR.sup.5 wherein R.sup.5 is hydrogen or lower alkyl and R.sup.6 is lower alkyl or phenyl;
- R.sup.3 is lower alkyl;
- R.sup.4 is oxo, ##STR15## wherein R.sup.13 is lower alkyl, lower alkoxy-lower alkylene, tetrahydropyranyl or teytrahydrofuryl, R.sup.14 is lower alkyl or phenyl and R.sup.15 and R.sup.16 are lower alkyl or taken together form lower alkylene or arylene of 6 to 10 carbon atoms, and n is 1 or 2, which comprises the steps of
- a. condensing a compound of the formula ##STR16## wherein R.sup.3, R.sup.4 and n are as hereinbefore defined with a compound of the formula ##STR17## wherein R.sup.7 and R.sup.8 independently and respectively are R.sup.1 and R.sup.2, nitro, benzyloxy, dephenylmethoxy or triphenylmethoxy, and R.sup.9 is hydrogen, cyano or COOR.sup.10 wherein R.sup.10 is lower alkyl or benzyl, in the presence of a base to give a compound of the formula ##STR18## wherein R.sup.3, R.sup.4, R.sup.7, R.sup.8 and n are as hereinbefore defined;
- b. saponifying and then decarboxylating a compound obtained in step (a) when R.sup.9 is cyano or COOR.sup.10 wherein R.sup.10 is a hereinbefore defined in the presence of alkali and then in the presence of acid to give a compound of the formula ##STR19## wherein R.sup.3, R.sup.4, R.sup.7, R.sup.8 and n are as hereinbefore defined, and
- c. hydrogenating a compound obtained in step (b) in the presence of a noble metal or nickel catalyst.
A process for the preparation of a compound of the formula ##STR21## wherein R.sup.1 and R.sup.2 independently are hydrogen, amino, OR.sup.5, OCOR.sup.6 or NHCOR.sup.5 wherein R.sup.5 is hydrogen or lower alkyl and R.sup.6 is lower alkyl or phenyl;
- R.sup.3 is lower alkyl;
- R.sup.4 is oxo, ##STR22## wherein R.sub.13 is lower alkyl, lower alkoxy-lower alkylene, tetrahydropyranyl or tetrahydrofuryl, R.sup.14 is lower alkyl or phenyl and R.sup.15 and R.sup.16 are lower alkyl or taken together form lower alkylene or arylene of 6 to 10 carbon atoms, and n is 1 or 2,
- which comprises the steps of
- a. condensing a compound of the formula ##STR23## wherein R.sup.3 is lower alkyl;
- R.sup.4 is oxo, ##STR24## wherein R.sup.13 is lower alkyl, lower alkoxy-lower alkylne, tetrahydropyranyl or tetrahydrofuryl, R.sup.14 is lower alkyl or phenyl and R.sup.15 and R.sup.16 are lower alkyl or taken together form lower alkylene or arylene of 6 to 10 carbon atoms;
- X is OR.sup.11, N(R.sup.12).sub.2, SR.sup.11, N.sup.+(R.sup.12).sub.3, ##STR25## or S.sup.+(R.sup.12).sub.2 wherein R.sup.11 is hydrogen, lower alkyl, acetyl or benzoyl, R.sup.12 is lower alkyl, and m is 1 or 2;
- and n is 1 or 2,
- with a compound of the formula ##STR26## wherein R.sup.7 and R.sup.8 independently and respectively are R.sup.1 and R.sup.2, nitro, benzyloxy, diphenylmethoxy or triphenylmethoxy, and R.sup.9 is hydrogen, cyano or COOR.sup.10 wherein R.sup.10 is lower alkyl or benzyl,
- in the presence of a base to give a compound of the formula ##STR27## wherein R.sup.3, R.sup.4, R.sup.7, R.sup.8 and n are as hereinbefore defined;
- b. saponifying and then decarboxylating a compound obtained in step (a) when R.sup.9 is cyano or COOR.sup.10 wherein R.sup.10 is as hereinbefore defined in the presence of alkali and then in the presence of acid to give a compound of the formula ##STR28## wherein R.sup.3, R.sup.4, R.sup.7, R.sup.8, R.sup.9 and n are as hereinbefore defined, and
- c. hydrogenating a compound obtained in step (b) in the presence of a noble metal or nickel catalyst.
Dependencies are inferred from the claim text.