Process for preparing butanetriol derivative

Abstract

A process for preparing a butanetriol derivative of the formula (1) useful as intermediates of medicines wherein R 1 is the same defined below, which comprises reacting a compound of the formula (3) wherein R 1 and R 2 are the different protecting groups, and an ethylene glycol derivative in a basic condition to prepare a compound of the formula (4) or (4 a ) wherein R 1 and R 2 are the same defined above, and then subjecting the compound (4) or (4 a ) to selective deprotection reaction.

1 . A process for preparing a butanetriol derivative of the formula (1)  
       
         
           
           
               
               
           
         
       
       which comprises subjecting a compound of the following formula (4) or (4a) to deprotection reaction  
       
         
           
           
               
               
           
         
       
       wherein in the above formulae, R 1  and R 2  are the different each other and are protecting groups for alcohol and said protecting groups such that only R 2  is removed when the deprotection reaction is carried out.  
     
     
         2 . A process for preparing a butanetriol derivative of the formula (1)  
       
         
           
           
               
               
           
         
       
       wherein R 1  is the same defined above, which comprises reacting a compound of the formula (3)  
       
         
           
           
               
               
           
         
       
       wherein R 1  and R 2  are the same defined above, and a compound of the formula (2)  
       
         
           
           
               
               
           
         
       
       wherein X is halogen atom or sulfonyloxy group, and R 2  is the same as defined above, 
 in a basic condition to prepare a compound of the formula (4)  
                     
 wherein R 1  and R 2  are the same defined above, and then subjecting the compound (4) to deprotection reaction.  
 
     
     
         3 . A process for preparing a butanetriol derivative of the formula (1)  
       
         
           
           
               
               
           
         
       
       wherein R 1  is the same defined above, which comprises reacting a compound of the formula (3)  
       
         
           
           
               
               
           
         
       
       wherein R 1  and R 2  are the same defined above, and a compound of the following formula (2a)  
       
         
           
           
               
               
           
         
       
       wherein X is halogen atom or sulfonyloxy group, or ethylene oxide in a basic condition to prepare a compound of the formula (4a)  
       
         
           
           
               
               
           
         
       
       wherein R 1  and R 2  are the same defined above, and then subjecting the compound (4a) to deprotection reaction.  
     
     
         4 . A process for preparing a compound (1) which comprises protecting primary hydroxy group for a compound of the formula (5)  
       
         
           
           
               
               
           
         
       
       wherein R 2  is the same as defined above, and then carrying out the process of claim ( 2 ) or claim ( 3 ).  
     
     
         5 . A process for preparing a compound (1) which comprises protecting a compound of the formula (7)  
       
         
           
           
               
               
           
         
       
       wherein R 3  and R 4  are the same or different and are hydrogen, C 1 -C 4  alkyl or phenyl, or may form a C 3 -C 6  cycloalkyl with the adjacent carbon atom, 
 with a protecting agent of alcohol to prepare a compound of the formula (6)  
                     
 wherein R 2 , R 3  and R 4  are the same as defined above, and then treating the compound (6) with an acid to prepare a compound (5) and then carrying out the process of claim ( 4 ).  
 
     
     
         6 . A process for preparing a compound (1) which comprises protecting primary hydroxy group for a compound of the formula (8)  
       
         
           
           
               
               
           
         
       
       wherein R 1  is the same as defined above, to prepare a compound (3) and then carrying out the process of claim ( 2 ) or claim ( 3 ).  
     
     
         7 . A process for preparing a compound (1) which comprises reducing a compound of the formula (9)  
       
         
           
           
               
               
           
         
       
       wherein R 5  is C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, phenyl, C 1 -C 6  alkyl substituted phenyl, aralkyl or 2-alkenyl, and R 1  is the same as defined above, 
 with an aluminum-reducing agent or a boron-reducing agent, to prepare a compound (8) and then carrying out the process of claim ( 6 ).  
 
     
     
         8 . A process for preparing a compound (1) which comprises protecting primary hydroxy group for a compound of the formula (10)  
       
         
           
           
               
               
           
         
       
       wherein R 1  is the same as defined above, to prepare a compound (9) and then carrying out the process of claim ( 7 ).  
     
     
         9 . The process for preparing a compound (1) according to any of  claims 1  to  8 , comprising using compound (3) and compound (4) or (4a), wherein the protecting groups, R 1  and R 2  in compounds (3) and (4) or (4a) are different each other and are protecting groups selected from the group of silyl ether-protecting groups, phenyl substituted methyl-protecting group and acetal-protecting groups, and that only R 2  is removed when the deprotection is carried out.  
     
     
         10 . The process for preparing a compound (1) according to  claim 9 , wherein the protecting groups, R 1  and R 2  in compounds (3) and (4) or (4a) are a silyl ether-protecting group and a phenyl substituted methyl-protecting group, respectively.  
     
     
         11 . The process for preparing a compound (1) according to  claim 9 , wherein the protective groups, R 1  and R 2  in compounds (3) and (4) or (4a) are a phenyl substituted methyl-protecting group and a silyl ether-protecting group, respectively.  
     
     
         12 . The process for preparing a compound (1) according to  claim 9 , wherein the protecting groups, R 1  and R 2  in compounds (3) and (4) or (4a) are a silyl ether-protecting group and an acetal-protecting group, respectively.  
     
     
         13 . The process for preparing a compound (1) according to  claim 9 , wherein the protecting groups, R 1  and R 2  in compounds (3) and (4) or (4a) are an acetal-protecting group and a silyl ether-protecting group, respectively.  
     
     
         14 . The process for preparing a compound (1) according to  claim 9 , wherein the protecting groups, R 1  and R 2  in compounds (3) and (4) or (4a) are a phenyl substituted methyl-protecting group and an acetal-protecting group, respectively.  
     
     
         15 . The process for preparing a compound (1) according to  claim 9 , wherein the protecting groups, R 1  and R 2  in compounds (3) and (4) or (4a) are an acetal-protecting group and a phenyl substituted methyl-protecting group, respectively.  
     
     
         16 . The process for preparing a compound (1) according to  claim 9 , wherein the protecting groups, R 1  and R 2  in compounds (3) and (4) or (4a) are trityl and benzyl, respectively.  
     
     
         17 . The process for preparing a compound (1) according to any of  claims 2  to  16 , comprising reacting compound (2), (2a) or ethylene oxide with compound (3) in an aprotic solvent.  
     
     
         18 . The process for preparing a compound (1) of  claim 17 , wherein the aprotic solvent is N,N-dimethylformamide or dimethyl sulfoxide.  
     
     
         19 . The process for preparing a compound (1) according to any of  claims 2  to  18 , comprising using an alkali metal hydride, hydroxide or carbonate as a base in reacting compound (2), (2a) or ethylene oxide with compound (3).  
     
     
         20 . The process for preparing an optically active compound (1) according to any of  claims 1  to  19 , comprising using a optically active starting material.  
     
     
         21 . A process for preparing a compound of the following formula (11) or its optically active compound  
       
         
           
           
               
               
           
         
       
       wherein R 6  is C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, phenyl, C 1 -C 6  alkyl, hologen-substituted phenyl or nitro-substituted phenyl and R 1  is the same as defined above, 
 which comprising preparing a compound (1) by the process of any of  claims 1  to  20  and then subjecting the compound to sulfonyl esterification.  
 
     
     
         22 . A compound of the following formula (3), (5) or (8) or its optically active compound  
       
         
           
           
               
               
           
         
       
       wherein R 1  and R 2  are the same as defined above.  
     
     
         23 . A compound of the following formula (4) or its optically active compound  
       
         
           
           
               
               
           
         
       
       wherein R 1  and R 2  are the same as defined above.  
     
     
         24 . A compound of the following formula (4a) or its optically active compound  
       
         
           
           
               
               
           
         
       
       wherein R 1  and R 2  are the same as defined above.