Process for the preparation of 2-(6-substituted-1,-3-dioxane-4-yl) acetic acid derivatives

Abstract

The invention relates to the preparation of 2-(6-substituted-1,3-dioxane-4-yl)acetic acid derivatives of formula (1), where X stands for a leaving group, and R 1 , R 2 , and R 3 each independently stand for an alkyl group with 1-3 carbon atoms from 4-hydroxy-6-X-substituted-methyl-tetrahydropyran-2-one compounds, where X is as defined above, with the aid of an acetalization agent, in the presence of an acid catalyst. The invention also relates to the novel compounds of formula (1) as well as salts and acids to be prepared from these, with the OR 3 group in formula (1) being replaced by an OY group, where X, R 1 and R 2 have the meanings defined above and where Y stands for an alkaline (earth) metal or a substituted or unsubstituted ammonium group or stands for hydrogen, and to the novel compounds of formula (2). The products concerned are, after conversion into the t-butyl ester of 2-(6-hydroxymethyl-1,3-dioxane-4-yl)acetic acid, important as intermediary products in the preparation of statins.

1 - 15 . (canceled) 
     
     
         16 . A compound having formula (2) in the (4R,6S) form, 
       
         
           
           
               
               
           
         
       
       wherein X is halo and where the compounds are in crystalline form. 
     
     
         17 . A compound according to  claim 16  where X is chloro, bromo or iodo. 
     
     
         18 . A compound having formula (2) in the (4R,6S) form, 
       
         
           
           
               
               
           
         
       
       wherein X is bromo. 
     
     
         19 . A crystalline compound which is (4R,6S)-4-hydroxy-6-chloromethyl-tetrahydropyran-2-one. 
     
     
         20 . A method for preparing (4R,6S)-4-hydroxy-6-chloromethyl-tetrahydropyran-2-one in crystalline form, the method comprising crystallizing the compound from ethyl acetate/heptane.