Crystalline1alpha,24(S)-dihydroxyvitamin D2 and method of purification thereof

Abstract

A method of purifying 1α,24(S)-dihydroxyvitamin D 2 to obtain 1α,24(S)-dihydroxyvitamin D 2 in crystalline form. The method includes the steps of boiling a solvent under inert atmosphere, dissolving a product containing 1α,24(S)-dihydroxyvitamin D 2 to be purified in the solvent, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of 1α,24(S)-dihydroxyvitamin D 2 crystals, and recovering the 1α,24(S)-dihydroxyvitamin D 2 crystals. The purification technique involves using one of several binary solvent systems, namely, acetone and hexane, 2-propanol and hexane, or ethyl formate and petroleum ether.

I claim:  
     
         1 . 1α,24(S)-dihydroxyvitamin D 2  in crystalline form.  
     
     
         2 . The three dimensional structure for 1α,24(S)-dihydroxyvitamin D 2  as illustrated in FIG. 6 herein and as defined by the atomic positional parameters set forth in Tables 1-7 herein.  
     
     
         3 . A method of purifying 1α,24(S)-dihydroxyvitamin D 2 , comprising the steps of: 
 (a) crystallizing 1α,24(S)-dihydroxyvitamin D 2  from a solvent; and  
 (b) recovering the crystallized 1α,24(S)-dihydroxyvitamin D 2 .  
 
     
     
         4 . The method of    claim 3    wherein said solvent is a binary system selected from the group consisting of an acetone and hexane mixture, a 2-propanol and hexane mixture, and an ethyl formate and petroleum ether mixture.  
     
     
         5 . The method of    claim 3    wherein said solvent comprises a binary system including acetone and hexane, and further including the steps of boiling said acetone, dissolving a product containing 1α,24(S)-dihydroxyvitamin D 2  in said boiling acetone, and thereafter adding said hexane to said boiling acetone containing said 1α,24(S)-dhydroxyvitmain D 2  prior to crystallizing the 1α,24(S)-dihydroxyvitamin D 2 .  
     
     
         6 . The method of    claim 3    wherein said solvent comprises a binary system including 2-propanol and hexane, and further including the steps of boiling a mixture of 2-propanol and hexane and dissolving a product containing 1α,24(S)-dihydroxyvitamin D 2  in said boiling mixture prior to crystallizing the 1α,24-dihydroxyvitamin D 2 .  
     
     
         7 . The method of    claim 3    wherein said solvent comprises a binary system including ethyl formate and petroleum ether, and further including the steps of boiling said ethyl formate, dissolving a product containing 1α,24(S)-dihydroxyvitamin D 2  in said boiling ethyl formate, and thereafter adding said petroleum ether to said boiling ethyl formate containing said 1α,24(S)-dihydroxyvitamin D 2  prior to crystallizing the 1α,24(S)-dihydroxyvitamin D 2 .  
     
     
         8 . The method of    claim 3    wherein the step of recovering comprises filtering.  
     
     
         9 . The method of    claim 3    further including the step of (c) repeating steps (a) and (b) using the recovered crystals from step (b).  
     
     
         10 . A method of purifying 1α,24(S)-dihydroxyvitamin D 2 , comprising the steps of: 
 (a) boiling acetone under inert atmosphere;  
 (b) dissolving a product containing 1α,24(S)-dihydroxvitamin D 2  to be purified in said boiling acetone to form a solution;  
 (c) adding hexane to said solution;  
 (d) cooling said solution below ambient temperature for a sufficient amount of time to form a precipitate of 1α,24(S)-dihydroxyvitamin D 2  crystals, and  
 (e) recovering the 1α,24(S)-dihydroxyvitamin D 2  crystals.  
 
     
     
         11 . The method of    claim 10    further including the step of allowing said solution to cool to ambient temperature prior to cooling below ambient temperature.  
     
     
         12 . The method of    claim 10    wherein said inert atmosphere is an argon atmosphere.  
     
     
         13 . The method of    claim 10    wherein said solution is cooled to between about 35° F. to about 45° F.  
     
     
         14 . The method of    claim 10    wherein the step of recovering comprises filtering.  
     
     
         15 . The method of    claim 10    further including the step of (f) repeating steps (a) through (e) using the recovered crystals from step (e) as the product of step (b).  
     
     
         16 . A method of purifying 1α,24(S)-dihydroxyvitamin D 2 , comprising the steps of: 
 (a) boiling 2-propanol-hexane mixture under inert atmosphere;  
 (b) dissolving a product containing 1α,24(S)-dihydroxyvitamin D 2  to be purified in said mixture to form a solution;  
 (c) cooling said solution below ambient temperature for a sufficient amount of time to form a precipitate of 1α,24(S)-dihydroxyvitamin D 2  crystals, and  
 (d) recovering the 1α,24(S)-dihydroxyvitamin D 2  crystals.  
 
     
     
         17 . The method of    claim 16    further including the step of allowing said solution to cool to ambient temperature prior to cooling below ambient temperature.  
     
     
         18 . The method of    claim 16    wherein said inert atmosphere is an argon atmosphere.  
     
     
         19 . The method of    claim 16    wherein said solution is cooled to between about 35° F. to about 45° F.  
     
     
         20 . The method of    claim 16    wherein the step of recovering comprises filtering.  
     
     
         21 . The method of    claim 16    further including the step of (e) repeating steps (a) through (d) using the recovered crystals from step (d) as the product of step (b).  
     
     
         22 . A method of purifying 1α,24(S)-dihydroxyvitamin D 2 , comprising the steps of: 
 (a) boiling ethyl formate under inert atmosphere;  
 (b) dissolving a product containing 1α,24(S)-dihydroxyvitamin D 2  to be purified in said boiling ethyl formate to form a solution;  
 (c) adding petroleum ether to said solution;  
 (d) cooling said solution below ambient temperature for a sufficient amount of time to form a precipitate of 1α,24(S)-dihydroxyvitamin D 2  crystals; and  
 (e) recovering the 1α,24(S)-dihydroxyvitamin D 2  crystals.  
 
     
     
         23 . The method of    claim 22    further including the step of allowing said solution to cool to ambient temperature prior to cooling below ambient temperature.  
     
     
         24 . The method of    claim 22    wherein said inert atmosphere is an argon atmosphere.  
     
     
         25 . The method of    claim 22    wherein said solution is cooled to between about 35° F. to about 45° F.  
     
     
         26 . The method    claim 22    wherein the step of recovering comprises filtering.  
     
     
         27 . The method of    claim 22    further including the step of (f) repeating steps (a) through (e) using the recovered crystals from step (e) as the product of step (b).