Process for precursors to calcitriol and related compounds
AssigneeHoffmann-La Roche Inc.
InventorsGeorge P. Yiannikouros, Percy S. Manchand
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Abstract
The process of the invention comprises reacting a C-22-halo-23,24-bisnorsteroid or C-22-halo-23,24-bisnor-9,10-secosteroid with a nickel complex of an electron withdrawing alkene of the formula ##STR1## wherein R.sub.1 is hydrogen, hydroxycarbonyl, lower alkoxycarbonyl, lower alkylcarbonyl or unsubstituted or substituted lower alkyl, and R.sub.2 is hydroxyl, lower alkoxy, or unsubstituted or substituted lower alkyl, to yield a C-25 or C-26 precursor of the formula ##STR2## which is appropriately functionalized for conversion into the corresponding steroid or secosteroid by treatment as hereinafter described.
Claims9
A process for the preparation of a compound of the formula ##STR14## wherein A is a 23,24-bisnorsteroid or a 23,24-bisnor-9,10-secosteroid radical, R.sub.1 is hydrogen, hydroxycarbonyl, lower alkoxycarbonyl, lower alkylcarbonyl or unsubstituted or substituted lower alkyl, R2 is hydroxyl, lower alkoxy, or unsubstituted or substituted lower alkyl, and R4 is lower alkyl,
- (1) which comprises reacting a compound of the formula ##STR15## with a nickel hydrate or, if unhydrated, in the presence of a proton source and a reducing agent;
- in the presence of an organic solvent and ligand source, and thereafter,
- (2) treating the reaction product of step 1, with a compound of the formula
- AX II
- wherein A is as previously described, and X is halogen to yield a compound of the formula ##STR16## (3) reacting the compound of formula IV with an organometallic reagent which adds R.sub.4, to yield the corresponding compound of formula I'.
Dependencies are inferred from the claim text.