Method for the preparation of thiadiazoles

Abstract

The present invention relates to processes for preparing protected glyceraldehydes, such as (hydroxy)methanesulfonates. In addition, the invention relates to thiadiazoles, particularly 3-diooxolanyl-thiadiazoles.

1 . (canceled) 
     
     
         2 . A process for preparing a [(4R)-2,2-dimethyl-1,3-dioxolan-4-yl](hydroxy) methanesulfonate salt comprising treatment of (R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde with a metasulfite salt. 
     
     
         3 . A process for preparing a compound of the formula 
       
         
           
           
               
               
           
         
       
       where R is aryl, alkyl, or the R groups together form a cycloalkyl, and X is a cation selected from Na + , H +  or K + , by the treatment of an aldehyde of the formula 
       
         
           
           
               
               
           
         
       
       where R is aryl, alkyl, or the R groups together form a cycloalkyl, with a metasulfite salt. 
     
     
         4 . The process of  claim 2  wherein the [(4R)-2,2-dimethyl-1,3-dioxolan-4-yl](hydroxy) methanesulfonate salt is sodium [(4R)-2,2-dimethyl-1,3-dioxolan-4-yl](hydroxy)m(Presently amended) ethanesulfonate. 
     
     
         5 . The process of  claim 2  wherein (R)2,2-dimethyl-1,3-dioxolane-4-carbaldehyde is the result of oxidative cleavage of 1,2,5,6-di-O-isopropylidene-D-mannitol. 
     
     
         6 . The process of  claim 5  wherein the oxidative cleavage occurs at a temperature between −15° C. and about 30° C. 
     
     
         7 . The process of  claim 5  wherein the oxidative cleavage occurs at about 20° C. 
     
     
         8 . The process of  claim 5  wherein the oxidative cleavage results from treatment of 1,2,5,6-di-O-isopropylidene-D-mannitol with NaIO 4 , or Pb(OAc) 4 . 
     
     
         9 . The process of  claim 5  wherein the oxidative cleavage results from treatment of 1,2,5,6-di-O-isopropylidene-D-mannitol with NaIO 4 . 
     
     
         10 . The process of  claim 5  comprising treatment of 1,2,5,6-di-O-isopropylidene-D-mannitol with NaIO 4  in an amount of at least about 1 equivalents per mole of 1,2,5,6-di-O-isopropylidene-D-mannitol. 
     
     
         11 . The process of  claim 5  comprising treatment of 1,2,5,6-di-O-isopropylidene-D-mannitol about 1.4-1.5 equivalents of NaIO 4  per mole of 1,2,5,6-di-O-isopropylidene-D-mannitol-. 
     
     
         12 . The process of  claim 5  wherein the oxidative cleavage takes place in the presence of NaHCO 3  and a mixture of CH 2 Cl 2  and H 2 O. 
     
     
         13 . The process of  claim 5  wherein the pH of the oxidative cleavage is maintained higher than 0.8. 
     
     
         14 . The process of  claim 2  wherein (R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde is treated with Na 2 S 2 O 5 , at a temperature above room temperature. 
     
     
         15 . The process of  claim 2  wherein (R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde is treated with Na 2 S 2 O 5  at a temperature above 35° C. 
     
     
         16 . The process of  claim 2  wherein t(R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde is treated with Na 2 S 2 O 5 , at a temperature of about 50° C. 
     
     
         17 . The process of  claim 2  wherein (R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde is treated with Na 2 S 2 O 5  in an amount of about 0.5-2 equivalents per mole of (R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde. 
     
     
         18 . The process of  claim 2  wherein (R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde is treated with about 0.5 equivalents of Na 2 S 2 O 5  per mole of (R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde. 
     
     
         19 . A compound of the structure 
       
         
           
           
               
               
           
         
       
     
     
         20 - 32 . (canceled) 
     
     
         33 . A process for preparing sodium [(4R)-2,2-dimethyl-1,3-dioxolan-4-yl](hydroxy) methanesulfonate, comprising:
 (a) treating 1,2,5,6-di-O-isopropylidene-D-mannitol with NaIO 4  in the presence of an aqueous NaHCO 3  buffer to provide (R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde; and   (b) treating (R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde with Na 2 S 2 O 5  at a temperature above 35° C.   
     
     
         34 . The process of  claim 33 , wherein 1,2,5,6-di-O-isopropylidene-D-mannitol is treated with about 1.4-1.5 equivalents of NaIO 4 . 
     
     
         35 . The process of  claim 34 , wherein 1,2,5,6-di-O-isopropylidene-D-mannitol with NaIO 4  at a pH above 3.0. 
     
     
         36 . The process of  claim 35 , wherein (R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde is treated with about 0.5 equivalents of Na 2 S 2 O 5 .