US2020024621A1PendingUtilityA1

Enzymatic process for the preparation of (1s,2r)-2-(difluoromethyl)-1-(propoxycarbonyl)cyclopropanecarboxylic acid

Assignee: ABBVIE INCPriority: Jan 30, 2015Filed: Jun 7, 2019Published: Jan 23, 2020
Est. expiryJan 30, 2035(~8.5 yrs left)· nominal 20-yr term from priority
C12P 41/005C12P 7/62C12Y 301/01003
57
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Claims

Abstract

Disclosed are methods of synthesizing enantioenriched difluoroalkylcyclopropyl amino esters and their salts, such as the dicyclohexylamine salt of (1S,2R)-2-(difluoromethyl)-1-(propoxycarbonyl)cyclopropane carboxylic acid. These compounds are useful intermediates in the synthesis of viral protease inhibitors.

Claims

exact text as granted — not AI-modified
1 - 57 . (canceled) 
     
     
         58 . A method according to the following reaction scheme: 
       
         
           
           
               
               
           
         
         wherein R is alkyl; t-BuOH is tert-butyl alcohol; Boc is tert-butoxycarbonyl; and DPPA is diphenylphosphoryl azide. 
       
     
     
         59 . The method of  claim 58 , wherein R is ethyl, propyl, or butyl. 
     
     
         60 . The method of  claim 59 , wherein R is n-propyl. 
     
     
         61 . The method of  claim 58 , wherein the starting material has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         62 . The method of  claim 58 , wherein the hydrolysis step comprises treatment with aqueous LiOH. 
     
     
         63 . A compound having the following structure, or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         64 . The compound of  claim 63 , wherein the compound has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         65 . The compound of  claim 64 , wherein R is ethyl, propyl, or butyl. 
     
     
         66 . The compound of  claim 65 , wherein R is n-propyl. 
     
     
         67 . The compound of  claim 64 , wherein the compound has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         68 . The compound of  claim 64 , wherein the compound has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         69 . The compound of  claim 68 , wherein R is ethyl, propyl, or butyl. 
     
     
         70 . The compound of  claim 69 , wherein R is n-propyl. 
     
     
         71 . A compound having the following structure, or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein R is alkyl; and Boc is tert-butoxycarbonyl. 
     
     
         72 . The compound of  claim 71 , wherein R is ethyl, propyl, or butyl. 
     
     
         73 . The compound of  claim 72 , wherein R is n-propyl. 
     
     
         74 . The compound of  claim 71 , wherein the compound has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         75 . The compound of  claim 74 , wherein R is ethyl, propyl, or butyl. 
     
     
         76 . The compound of  claim 75 , wherein R is n-propyl. 
     
     
         77 . A compound having the following structure, or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein Boc is tert-butoxycarbonyl. 
     
     
         78 . The compound of  claim 77 , wherein the compound has the following structure:

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