Process for the preparation of fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl) ethyl ether

A process for the preparation of fluoromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether (sevoflurane) which consists of the following steps:

• (i) reacting hexafluoroisopropanol with paraformaldehyde, sulfuric acid and thionyl chloride to form the intermediate sevochlorane, wherein said step is carried out by:
• a) adding the hexafluoroisopropanol (HFIP), 1.5 molar equivalents of paraformaldehyde and 1.8 molar equivalents of thionyl chloride per molar equivalent of HFIP to a reaction vessel;
• b) adding 1.5 molar equivalents of sulfuric acid per molar equivalent of HFIP, under stirring, to the reaction mixture of item a), maintaining the reaction temperature below 20° C. until this step is completed;
• c) maintaining the reaction mixture under stirring at a temperature ranging between 0° C. and 60° C.;
• d) separating a resulting organic phase comprising sevochlorane;
• (ii) treating the organic phase comprising sevochlorane with an aqueous solution of sodium carbonate to neutralization;
• (iii) treating the neutral organic phase comprising sevochlorane with an aqueous solution of sodium hydroxide to decompose and remove by-products;
• (iv) converting the sevochlorane to sevoflurane by reacting the sevochlorane with potassium fluoride (KF) in the presence of 0.15 molar equivalents of potassium iodide per molar equivalent of sevochlorane, and a solvent;
• (v) isolating the sevoflurane by addition of water, separation of the organic phase and distillation, or by direct distillation of the reaction mixture;
• and
• (vi) purifying the sevoflurane by fractional distillation.