Improvements in the two-step synthesis of 1,1,1,3,3,3-hexafluoro-2- (fluoromehoxy)propane (Sevoflurane) that result in the product cost reduction, safety level enhancement and positive environmental impacts are described. This process consists of chloromethylation reaction of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) followed by a halogen-exchange fluorination. This is the first synthesis of Sevoflurane in Iran which was successfully scaled up. During this work, several improvements have been achieved by optimization of the reaction time, the amount of consumed starting materials and solvents and work up procedure while keeping the yield and purity intact. The reaction time of the first step (24 h) was diminished to 4 h. (19)F NMR spectroscopy was used to investigate the rate of the reaction in the first step and to evaluate the influence of different parameters mentioned on the achieved improvements.
Keywords: Halogen-exchange fluorination; Hexafluoro-2-propanol; Inhalation anesthetic; Sevoflurane.