Industrial preparation method of sevoflurane

Abstract

The invention discloses an industrial preparation method of sevoflurane. The method comprises the following steps: adding chloromethyl ether and alkali metal fluoride to a solvent, uniformly stirring and heating for a reflux reaction; after the reaction, cooling a reaction liquid to be less than 20 DEG C and filtering, combining a filtrate with reaction residual liquor and distilling under normal pressure; collecting fraction less than 80 DEG C so as to obtain crude sevoflurane, and rectifying so as to obtain a finished sevoflurane product. By optimizing the crude sevoflurane preparing step, namely adding a filtering and impurity removing step after fluoridation reaction, the industrial preparation method disclosed by the invention can be used for relieving a side reaction during distilling and avoiding the generation of some impurities, and especially impurities similar to the sevoflurane in retention time, so that rectifying difficulty is reduced, rectifying time is reduced and product quality is guaranteed; the content of the finished sevoflurane product can reach 99.999%, so that manpower and material resources can be saved and product yield can be improved to 92.4%; and meanwhile, generated cauldron bottom residue can be recycled, so that the industrial preparation method can be used for further improving yield and reducing cost, and the preparation method is more conducive to industrial production.

Description

technical field [0001] The invention relates to a preparation method of an inhalation anesthetic sevoflurane. Background technique [0002] Sevoflurane (1), the chemical name is 1,1,1,3,3,3-hexafluoro-2-fluoromethoxypropane, which is an ideal choice after halothane, enflurane and isoflurane. The inhalational anesthetic, which was approved by the US FDA in 1995, has short induction period, fast recovery, easy metabolism, low blood gas distribution coefficient, stable hemodynamics, small adverse reactions to the human body, easy adjustment of anesthesia depth, and non-flammable and explosive Etc. Therefore, it has been paid more and more attention and adopted in general anesthesia of operation, and has a broad market prospect. [0003] The most commonly used raw material in the synthetic method of sevoflurane is 1,1,1,3,3,3-hexafluoroisopropanol (hereinafter referred to as hexafluoroisopropanol), Bernad M Regan et al. in US Patents US3683092 and US3689571 It is reported th...

AI Technical Summary

Problems solved by technology

Research has found that the direct distillation of solid-liquid mixed feed liquid is not conducive to industrial production: on the one hand, the temperature in the still gradually increases, and the boiling point of the received fraction gradually decreases, indicating that the residual solid and liquid in the still have side reactions, resulting in low-boiling It is a new impurity, and as the temperature rises, the impurity content increases. From the observation of the gas chromatogram, the retention time of this impurity is close to that of sevoflurane, and it is not easy to remove in the subsequent rectification process. Repeated rectification is required, which consumes man-hours and affects product yield. rate, which increases the production cost; on the other hand, most of the residue in the still is carbonized solid, which cannot be recycled, is difficult to handle, and causes great environmental pollution.