US2002052527A1PendingUtilityA1

Novel process for preparing alendronic acid

43
Priority: Feb 17, 1999Filed: Mar 20, 2001Published: May 2, 2002
Est. expiryFeb 17, 2019(expired)· nominal 20-yr term from priority
Inventors:Ramy Lidor-HadasRevital Lifshitz
A61P 19/08C07F 9/3873C07F 9/38
43
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Claims

Abstract

A novel process for the preparation of alendronic acid is disclosed. The method comprises the steps of reacting a compound of formula I with H 3 PO 3 wherein R is an imido group and R 1 is selected from the group consisting of chloro, bromo, iodo, fluoro, hydroxy, amino, —OR 2 or —OC(O)R 2 , wherein R 2 is C 1 -C 12 alkyl, C 1 -C 12 cycloalkyl or C 1 -C 12 aryl; and then reacting the product of the first step with a deprotecting agent. Alendronic acid is then recovered. The method is safe, efficient and suitable for use on a large scale.

Claims

exact text as granted — not AI-modified
We claim:  
     
         1 . A process for the preparation of alendronic acid, which comprises the steps of: 
 a) reacting a compound of the formula I with H 3 PO 3                             wherein 
 R is an imido group; and  
 R 1  is selected from the group which consists of chloro, bromo, iodo, fluoro, hydroxy, amino, —OR 2  or —OC(O)R 2 , wherein R 2  is C 1 -C 12  alkyl, C 1 -C 12  cycloalkyl, or C 1 -C 12  aryl;  
   b) reacting the product of step (a) with a deprotecting agent; and    c) recovering alendronic acid.    
     
     
         2 . A process according to  claim 1  wherein R is selected from the group which consists of N-phthalimido and N-maleimido.  
     
     
         3 . A process according to  claim 1  wherein R 1  is selected from the group which consists of chloro, bromo and hydroxy.  
     
     
         4 . A process according to  claim 1  wherein step (a) further comprises the use of one or more of the compounds selected from the group which consists of H 3 PO 4 , PCl 3 , PCl 5  and POCl 3 .  
     
     
         5 . A process according to  claim 1  wherein step (b) comprises using one or more deprotecting agents selected from the group which consists of HCl, HBr, acetic acid, H 3 PO 3 , and H 3 PO 4 .  
     
     
         6 . A process according to  claim 1 , wherein steps (a) and (b) take place in a single vessel.  
     
     
         7 . A process according to  claim 1  in which step (a) is performed at the temperature of between about 25° C. and about 180° C.  
     
     
         8 . A process according to  claim 7  in which step (a) is performed at the temperature of between about 80° and about 140° C.  
     
     
         9 . A process according to  claim 1  in which step (b) is performed at the temperature of between about 25° C. and about 130° C.  
     
     
         10 . A process according to  claim 9  in which step (b) is performed at the temperature of between about 100° C. and about 130° C.  
     
     
         11 . A process according to  claim 6  which is performed at the temperature of between about 25° C. and about 180° C.  
     
     
         12 . A process according to  claim 11  which is performed at the temperature of between about 80° C. and about 140° C.  
     
     
         13 . A process according to  claim 1  wherein the molar ratio between the compound of formula I and H 3 PO 3  is between 1:1 and 1:6.  
     
     
         14 . A process according to  claim 13  wherein the molar ratio between the compound of formula I and H 3 PO 3  is between 1:2 and 1:5.  
     
     
         15 . A process according to  claim 4  wherein the molar ratio between the compound of formula I and PCl 3  is between 1:1 and 1:6.  
     
     
         16 . A process according to  claim 15  wherein the molar ratio between the compound of formula I and PCl 3  is between 1:2 and 1:3.  
     
     
         17 . A process according to  claim 4  wherein the molar ratio between the compound of formula I and H 3 PO 4  is between 1:1 and 1:6.  
     
     
         18 . A process according to  claim 17  wherein the molar ratio between the compound of formula I and H 3 PO 4  is between 1:2 and 1:4.  
     
     
         19 . A process according to  claim 4  wherein the molar ratio between the compound of formula I and PCl 5  is between 1:1 and 1:6.  
     
     
         20 . A process according to  claim 19  wherein the molar ratio between the compound of formula I and PCl 5  is between 1:2 and 1:3.  
     
     
         21 . A process according to  claim 4  wherein the molar ratio between the compound of formula I and POCl 3  is between 1:1 and 1:6.  
     
     
         22 . A process according to  claim 21  wherein the molar ratio between the compound of formula I and POCl 3  is between 1:2 and 1:3.  
     
     
         23 . Alendronic acid prepared according to the process of  claim 1.

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