Continuous synthesis method for 2-fluoroethyl malonate compound

Abstract

The invention discloses a continuous synthesis method for a 2-fluoroethyl malonate compound. The continuous synthesis method comprises the following steps: taking a formula shown in the description asa raw material, and carrying out a continuous decarbonylation reaction in continuous reaction equipment, thereby obtaining the 2-fluoroethyl malonate compound represented by a formula shown in the description, wherein R and R' separately represent straight-chain or branched alkyl, substituted or unsubstituted aryl or substituted or unsubstituted heterocycle or cyclic alkyl and are the same or different. According to the method, the high-temperature decarbonylation reaction of 2-fluoro-3-oxo-disuccinate is achieved by adopting the continuous reaction equipment. Compared with the traditional pot type reaction, the amount of materials participating in reaction in unit time is reduced greatly, so that a high-temperature hazardous area is reduced, and the security risk is greatly lowered.

Description

technical field [0001] The invention relates to the field of medicine and chemical industry, in particular to a continuous synthesis method of 2-fluoromalonate diester compounds. Background technique [0002] 2-fluoromalonate diester is an important class of fluorine-containing organic intermediates, which can undergo a series of reactions such as alkylation, alkoxylation, and hydroxyalkylation, and is widely used in organic synthesis, medicine, pesticides, The production of spices, dyes, etc. can also be used to prepare amino acids, which are widely used in biochemical research. Therefore, 2-fluoromalonate diester derivatives have extremely broad fields and very broad development prospects, and it is of great significance to develop a high-efficiency, low-cost 2-fluoromalonate diester synthesis process. [0003] At present, the methods for preparing 2-fluoromalonate diester mainly include the following: carbonyl elimination method, esterification method, cracking method an...

AI Technical Summary

Problems solved by technology

The main disadvantage of this method is that the raw materials are highly toxic, highly corrosive to equipment, and have high requirements for reaction equipment. During the reaction, dichloromalonate and dichloromalonate diester will be produced, which will affect product quality and yield.

In addition, in the post-treatment process, triethylamine is difficult to recover and a large amount of nitrogen-containing wastewater is produced, which is troublesome to deal with and causes great pollution to the environment.

[0005] Chinese patent (CN 102531897) provides a method for preparing diethyl 2-fluoromalonate, which uses ethyl fluoroacetate and diethyl oxalate as initial raw materials, and synthesizes 2 through two steps of condensation and oxidation. - diethyl fluoromalonate, the total yield is 32.5%, this method still has the problem of low yield and many "three wastes"

[0006] Chinese patent (CN 107935853) provides a new method for preparing diethyl 2-fluoromalonate, which uses ethyl fluoroacetate, diethyl carbonate and sodium hydride as initial raw materials to synthesize 2-fluoromalonic acid Diethyl ester, the total yield is 52.3%. Compared with this method, the yield is higher, but the main disadvantage of this process is that sodium hydride is used, which will produce a large amount of hydrogen when used in the production process, which is very dangerous. It does not have the capacity of industrial production, and needs to use a large amount of diethyl carbonate, and it is difficult to recover diethyl carbonate in the post-treatment process

[0007] In addition, most of the traditional processes use tank reactors. If high temperature and high pressure reactions are required, there are great safety risks in traditional tank reactions, and the requirements for equipment are also high, which is not suitable for industrialized large-scale production.

At the same time, the traditional kettle-type process takes a long time to react, often requiring more than ten hours or even a few days, and the production efficiency is low

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