Method for the preparation of sevoflurane

Abstract

A method for the preparation of (CF 3 ) 2 CHOCH 2 F (Sevoflurane) is presented, which comprises providing a mixture of (CF 3 ) 2 CHOCH 2 Cl, potassium fluoride, water, and a phase transfer catalyst and reacting the mixture to form (CF 3 ) 2 CHOCH 2 F.

1 - 16 . (canceled) 
     
     
         17 . A product mixture comprising sevoflurane, sevochlorane and sevochlorane hydrolysis products from the process for the preparation of sevoflurane comprising combining, in a reaction vessel, components comprising (CF 3 ) 2 CHOCH 2 Cl, potassium fluoride, water, and a phase transfer catalyst, and without the presence of an organic co-solvent, wherein the phase transfer catalyst is selected from the group consisting of: quaternary ammonium salts, quaternary phosphonium salts, and crown ethers, to form a reaction mixture wherein the molar amount of potassium fluoride per mole of (CF 3 ) 2 CHOCH 2 Cl added is greater than 0.1:1, the phase transfer catalyst is present in amounts greater than 0.25% based upon the weight of the (CF 3 ) 2 CHOCH 2 Cl charged to the reaction vessel, and the water is present in amounts such that the weight of potassium fluoride to the combined weight of potassium fluoride and water is greater than 25%; wherein sevoflurane is formed. 
     
     
         18 . A product mixture as in  claim 17 , wherein less than 5 wt % of the (CF 3 ) 2 CHOCH 2 Cl charged to the reaction vessel is hydrolyzed. 
     
     
         19 . A product mixture as in  claim 17 , wherein greater than 50% of the molar amount of (CF 3 ) 2 CHOCH 2 Cl consumed in the reaction is converted to sevoflurane. 
     
     
         20 . A product mixture as in  claim 17  wherein the reaction mixture further comprises potassium bifluoride (KHF 2 ) or a potassium fluoride hydrate salt. 
     
     
         21 . A product mixture as in  claim 17  wherein the mixture further comprises hydrochloric acid, hydrofluoric acid, or another inorganic or organic acid at an amount in the range of 1 to 3% based upon the weight of (CF 3 ) 2 CHOCH 2 Cl charged to the reaction vessel. 
     
     
         22 - 25 . (canceled)