Process for the synthesis of vitamin D compounds and intermediates for the synthesis of the compounds

摘要

An object of the present invention is to provide a process for synthesizing a vitamin D compound by simple procedures at lower costs.;The present invention provides a process for preparing a vitamin D compound and an intermediate thereof, comprising the step of: (a) mixing a ketone or aldehyde, a Wittig reagent, and a base; or (b) mixing a ketone or aldehyde and a Wittig reagent, and then adding a base to the resulting mixture.

主权项

1. A process for preparing a vitamin D compound
of formula (I) and an intermediate thereof: wherein R1 and R2 are the same as R5 and R6 defined below, respectively, and R3 is the same as R8 defined below, comprising the steps of: (a) mixing a ketone of formula (II):
R5COR6  (II) wherein R5 and R6 are joined to form a bicyclo[4.3.0]nonanyl having one or more substituents or a bicyclo[4.3.0]nonenyl having one or more substituents, with an allylphosphine oxide derivative of formula (IV):wherein R8 represents a cyclohexanyl optionally substituted and optionally containing one or more double bonds, in a solvent having no influence on the reaction between the ketone and the allylphosphine oxide derivative;
(b) evaporating the mixture to dryness to remove water, and dissolving the residue in another solvent; (c) cooling the resulting solution to a temperature of about −20° C. to room temperature; and (d) adding a base dropwise to the solution at a temperature of about −20° C. to room temperature; wherein the cyclohexanyl represented by R8 is optionally substituted with one or more substituents selected from the group consisting of hydroxy, ═CH2, and a C1-C15 straight or branched hydrocarbon optionally containing an intervening oxygen, where the straight or branched hydrocarbon may be substituted with one or more hydroxyl groups; and wherein the substituents on R5, R6, and R8 may be protected by a protective group.