Method for synthesizing 2-fluorocyclopropane carboxylic acid

Abstract

Disclosed is a new method for synthesizing 2-fluorocyclopropanecarboxylic acid comprising: 1) performing reaction of 1,1-dichloro-1-fluoroethane with thiophenol in the presence of an alkali, to produce a phenyl sulfide intermediate; 2) performing oxidation reaction of the phenyl sulfide intermediate with Oxone; 3) performing elimination reaction of the product of Step 2) in the presence of an alkali, to obtain 1-fluoro-1-benzenesulfonyl ethylene; 4) performing addition reaction of the 1-fluoro-benzenesulfonyl ethylene with ethyl diazoacetate in the presence of a catalyst, to obtain a cyclopropane intermediate; 5) performing elimination reaction of the cyclopropane intermediate in the presence of an alkali before acidification, to obtain 2-fluorocyclopropanecarboxylic acid. Herein, the synthetic route is short, used materials are bulk commodities, and raw materials are inexpensive and readily available. The process can be safely scaled up by replacing commonly used mCPBA reagents with Oxone. Further, reaction yield is improved, production cost is greatly reduced, and operation is simplified.

What is claimed is: 
     
       1. A new method for synthesizing 2-fluorocyclopropanecarboxylic acid, comprising the following steps:
 1) performing a reaction of 1,1-dichloro-1-fluoroethane with thiophenol in the presence of an alkali, to produce a phenyl sulfide intermediate; 
 2) performing an oxidation reaction of the phenyl sulfide intermediate with Oxone; 
 3) performing an elimination reaction of a product obtained in Step 2) in the presence of an alkali, to obtain 1-fluoro-1-benzenesulfonyl ethylene; 
 4) performing an addition reaction of the 1-fluoro-1-benzenesulfonyl ethylene and ethyl diazoacetate in the presence of a catalyst, to obtain a cyclopropane intermediate; 
 5) performing an elimination reaction of the cyclopropane intermediate in the presence of an alkali before an acidification, to obtain 2-fluorocyclopropanecarboxylic acid. 
 
     
     
       2. The new method for synthesizing 2-fluorocyclopropanecarboxylic acid of  claim 1 , wherein, the alkali of Step 1) is at least one selected from alkoxide, carbonate, bicarbonate, hydroxide, and hydride of an alkali metal or alkaline earth metal. 
     
     
       3. The new method for synthesizing 2-fluorocyclopropanecarboxylic acid of  claim 2 , wherein, in the step 1), the mass ratio of 1,1-dichloro-1-fluoroethane and thiophenol is (1.1-3.5):1. 
     
     
       4. The new method for synthesizing 2-fluorocyclopropanecarboxylic acid of  claim 1 , wherein, in the step 2), the mass ratio of the phenyl sulfide intermediate and Oxone is 1:(7-9). 
     
     
       5. The new method for synthesizing 2-fluorocyclopropanecarboxylic acid of  claim 1 , wherein, the alkali of Step 3) is at least one selected from alkoxide, carbonate, bicarbonate, hydroxide and hydride of an alkali metal or alkaline earth metal, and DBU. 
     
     
       6. The new method for synthesizing 2-fluorocyclopropanecarboxylic acid of  claim 5 , wherein, in Step 3), the mass ratio of the product obtained in step 2) and the alkali is (1.1-2): 1. 
     
     
       7. The new method for synthesizing 2-fluorocyclopropanecarboxylic acid of  claim 1 , wherein, in Step 4), the mass ratio of 1-fluoro-1-benzenesulfonylethylene and ethyl diazoacetate is (1.1-1.7):1. 
     
     
       8. The new method for synthesizing 2-fluorocyclopropanecarboxylic acid of  claim 1 , wherein, the catalyst of Step 4) is a rhodium-based catalyst. 
     
     
       9. The new method for synthesizing 2-fluorocyclopropanecarboxylic acid of  claim 1 , wherein, the alkali of Step 5) is at least one selected from alkoxide, carbonate, bicarbonate, hydroxide, and hydride of an alkali metal or alkaline earth metal. 
     
     
       10. The new method for synthesizing 2-fluorocyclopropanecarboxylic acid of  claim 9 , wherein, in the step 5), an acid for the acidification is at least one selected from hydrochloric acid, sulfuric acid, nitric acid and perchloric acid.