ASYMMETRIC PREPARATION OF 1,2,2,2-TETRAFLUOROETHYL METHYL-ETHER, AN INTERMEDIATE IN THE SYNTHESIS OF VOLATILE ANESTHETICS

1-Methoxytetrafluoropropionic acid (2) is resolved by diastereomeric amide formation with (S)-(-)-1-phenethylamine/chromatography/hydrolysis. Both enantiomers are obtained in greater than or equal to 99% ee. Conversion of each enantiomeric acid to its potassium salt followed by thermolysis in triethylene glycol/1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) gives the enantiomers of 1,2,2,2-tetrafluoroethyl methyl ether (1) with a very high degree of stereospecificity. The use of DMPU as co-solvent results in a significant yield improvement.