US2015210620A1PendingUtilityA1

Process for the preparation of vitamin k2

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Assignee: KAPPA BIOSCIENCE ASPriority: Sep 24, 2008Filed: Apr 8, 2015Published: Jul 30, 2015
Est. expirySep 24, 2028(~2.2 yrs left)· nominal 20-yr term from priority
C07C 315/04C07C 43/215C07C 41/22C07C 41/26C07C 41/30C07C 17/16C07B 2200/13C07C 21/215C07C 46/02C07C 319/20C07C 50/14C07C 41/18C07C 46/04C07C 317/14C07C 46/00
55
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Claims

Abstract

Using a combination of Kumada, Suzuki and Biellmann chemistry, various menaquinones can synthesised rapidly and with stereochemical integrity offering a new way of preparing these vitamin K2 components for the pharmaceutical market. In one embodiment a process for the preparation of a compound of formula (I) is defined including a step in which (i) a compound of formula (II) is reacted with a compound of formula (III) wherein R is an alkyl group; LG is a leaving group; m is an integer from 0 to 8; n is an integer of from 0 to 9; and X is hydrogen, halide, hydroxyl or protected hydroxyl; in the presence of a copper, nickel or palladium catalyst.

Claims

exact text as granted — not AI-modified
1 - 9 . (canceled) 
     
     
         10 . A compound 
       
         
           
           
               
               
           
         
         wherein R is an alkyl group. 
       
     
     
         11 . The compound as claimed in  claim 10  of formula 
       
         
           
           
               
               
           
         
       
     
     
         12 . A process for the preparation of MK-7 comprising converting a compound 
       
         
           
           
               
               
           
         
         wherein R is an alkyl group into MK-7: 
       
       
         
           
           
               
               
           
         
       
     
     
         13 . The process as claimed in  claim 12  wherein conversion is achieved using cerium ammonium nitrate. 
     
     
         14 . A process for the preparation of a compound of formula (I) 
       
         
           
           
               
               
           
         
         wherein n is 1 to 9; 
         comprising (i) deprotonating alpha to the sulphur a compound of formula: 
       
       
         
           
           
               
               
           
         
         wherein R is an alkyl group; and 
         Ar is an aryl group such as phenyl; 
         and reacting with a compound of formula 
       
       
         
           
           
               
               
           
         
         wherein m is 0 to 8; and 
         LG is a leaving group; to obtain 
       
       
         
           
           
               
               
           
         
         (ii) reducing the SAr or —SO 2 Ar to hydrogen to give diprotected naphthoquinone: 
       
       
         
           
           
               
               
           
         
       
       and
 (iii) converting the diprotected naphthoquinone into a naphthoquinone ring. 
 
     
     
         15 . The process as claimed in  claim 14  wherein the deprotonation step (i) is achieved using BuLi. 
     
     
         16 . The process as claimed in  claim 14  wherein Ar is Ph. 
     
     
         17 . The process as claimed in  claim 14  wherein LG is a halide. 
     
     
         18 . The process as claimed in  claim 14  wherein the step (iii) reduction uses cerium ammonium nitrate. 
     
     
         19 . The process as described in  claim 14  wherein the compound of formula (I) is MK-7. 
     
     
         20 . A process for the preparation of a compound of formula (I) 
       
         
           
           
               
               
           
         
         comprising (i) deprotonating alpha to the sulphur a compound of formula 
       
       
         
           
           
               
               
           
         
         wherein R is an alkyl group; and 
         Ar is an aryl group such as phenyl; 
         and reacting with a compound of formula 
       
       
         
           
           
               
               
           
         
         wherein m is 4; and 
         LG is a leaving group; to obtain 
       
       
         
           
           
               
               
           
         
         (ii) reducing the SAr or —SO 2 Ar to hydrogen to give diprotected naphthoquinone: 
       
       
         
           
           
               
               
           
         
       
       and
 (iii) converting the diprotected naphthoquinone into a naphthoquinone ring. 
 
     
     
         21 . A process for the preparation of a compound of formula (I) 
       
         
           
           
               
               
           
         
         comprising deprotonating alpha to the sulphur a compound of formula 
       
       
         
           
           
               
               
           
         
         wherein R is an alkyl group; and 
         Ar is an aryl group such as phenyl; 
         and reacting with a compound of formula 
       
       
         
           
           
               
               
           
         
       
       wherein LG is a leaving group; to obtain 
       
         
           
           
               
               
           
         
         (ii) reducing the SAr or —SO 2 Ar to hydrogen and 
         (iii) converting the diprotected naphthoquinone into a naphthoquinone ring. 
       
     
     
         22 . A process for the preparation of a compound of formula (I) 
       
         
           
           
               
               
           
         
         comprising deprotonating alpha to the sulphur a compound of formula 
       
       
         
           
           
               
               
           
         
         wherein R is an alkyl group; and 
         Ar is an aryl group such as phenyl; 
         and reacting with a compound of formula 
       
       
         
           
           
               
               
           
         
       
       wherein LG is a leaving group; to obtain 
       
         
           
           
               
               
           
         
         (ii) reducing the SAr or —SO 2 Ar groups to hydrogen to form diprotected naphthoquinone 
       
       
         
           
           
               
               
           
         
       
       and
 (iii) converting the diprotected naphthoquinone into a naphthoquinone ring.

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