Crystals of a vitamin D derivative and a method for the preparation thereof

Abstract

The present invention provides crystals of the compound represented by formula (I): crystals of a vitamin D derivative which are obtained by purifying a crude or preliminarily purified product of the vitamin D derivative through a reverse phase chromatography and then crystallizing the purified derivative from an organic solvent; novel compounds which are formed during the synthesis of a vitamin D derivative as by-product; and a method for purifying a vitamin D derivative or the precursor thereof. The method of the present invention makes it possible to supply a highly purified vitamin D derivative, especially ED-71, in bulk and steadily.

1 . A method for purifying the compound represented by formula (II):  
       
         
           
           
               
               
           
         
         comprising recrystallizing a crude or preliminarily purified product of the compound represented by formula (II) from an alcohol.  
       
     
     
         2 . The method according to  claim 1  wherein the alcohol is methanol.  
     
     
         3 . A purified product of the compound represented by formula (II)  
       
         
           
           
               
               
           
         
         which is obtained by recrystallizing a crude or preliminarily purified product of the compound represented by formula (II) from an alcohol.  
       
     
     
         4 . The method according to  claim 3  wherein the alcohol is methanol.  
     
     
         5 . A method for preparing a purified product of the vitamin D derivative represented by formula (I):  
       
         
           
           
               
               
           
         
       
       comprising: 
 recrystallizing a crude or preliminarily purified product of the compound represented by formula (II)  
                     
  from an alcohol;  
 subjecting the recrystallized compound of formula (II) to ultraviolet light radiation and then a thermal isomerization reaction to produce a vitamin D derivative represented by formula (I);  
 purifying the crude or preliminarily purified vitamin D derivative of formula (I) using reverse phase chromatography; and  
 crystallizing the vitamin D derivative of formula (I) from an organic solvent.  
 
     
     
         6 . The method according to  claim 5  wherein the organic solvent is an aprotic organic solvent.  
     
     
         7 . The method according to  claim 6  wherein the aprotic organic solvent is ethyl acetate, acetone, acetonitrile, or mixtures thereof.  
     
     
         8 . The method according to  claim 5  wherein the alcohol is methanol.  
     
     
         9 . The method according to  claim 6  wherein the alcohol is methanol.  
     
     
         10 . The method according to  claim 7  wherein the alcohol is methanol.  
     
     
         11 . The method according to  claim 8  wherein the alcohol is methanol.  
     
     
         12 . A compound represented by formula (III):  
       
         
           
           
               
               
           
         
       
     
     
         13 . A compound represented by formula (IV):