One-step preparation method of ethyl 4-bromobutyrate

Abstract

The invention belongs to the technical field of preparation of ethyl 4-bromobutyrate, and provides a one-step preparation method of ethyl 4-bromobutyrate, which comprises the following steps: step 1, adding gamma-butyrolactone into a container under the conditions of water bath and constant-speed stirring, and controlling the temperature of the water bath to be 10-30 DEG C; step 2, slowly introducing dry hydrogen bromide gas; step 3, after the hydrogen bromide gas is completely introduced, controlling the reaction temperature to be 0-50 DEG C, and continuously stirring and reacting for 1-3 hours; step 4, adding absolute ethyl alcohol, and controlling the constant temperature of the water bath at 10-90 DEG C to finish the reaction; step 5, after the reaction is finished, adding a proper amount of deionized water for washing, fully stirring, standing for layering, taking a lower organic phase, adding a NaHCO3 saturated solution, adjusting the pH value to 7.0, standing for layering, taking the lower organic phase, washing with deionized water, fully stirring, standing for layering, and separating out an organic layer; and 6, adding a drying agent, and drying to obtain the ethyl 4-bromobutyrate. The one-step preparation method of ethyl 4-bromobutyrate is suitable for industrial large-scale production.

Description

technical field [0001] The invention belongs to the technical field of preparation of ethyl 4-bromobutyrate, in particular to a one-step preparation method of ethyl 4-bromobutyrate. Background technique [0002] Ethyl 4-bromobutyrate is an important intermediate for pesticides, medicines and other pharmaceuticals. It is indispensable in the preparation of pesticides and medicines, such as: talixol for Parkinson's syndrome, ezetimibe for hypercholesterolemia, bepotastine for Meniere's syndrome and Intermediates of tolvaptan 7-chloro-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one, etc. [0003] Among the common synthetic methods reported at present, there are three synthetic methods using 4-bromobutyric acid or γ-butyrolactone as raw materials. [0004] The first is the literature Journal of Medicinal Chemistry, 2017, 60, 608; ChemPhysChem, 2019, 20, 1690, etc. reported using 4-bromobutyric acid as a raw material, using p-toluenesulfonic acid or oxalyl chloride as a catalyst, and ...

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Problems solved by technology

[0004] The first one is reported in the literature Journal of Medicinal Chemistry, 2017, 60, 608; ChemPhysChem, 2019, 20, 1690, etc., using 4-bromobutyric acid as a raw material, using p-toluenesulfonic acid or oxalyl chloride as a catalyst, and ethanol through esterification The reaction prepares ethyl 4-bromobutyrate. The shortcoming of this method is that the post-treatment of the catalyst required for the reaction is cumbersome and the yield is low, and it is easy to pollute the environment. The most important thing is that there are many raw materials for the synthesis of 4-bromobutyrate It uses γ-butyrolactone as the raw material and needs two steps to complete;

[0005] The second kind is the method that the report such as patent CN1453263, CN1218927C uses gamma-butyrolactone as raw material, the method for preparing with red phosphorus, bromine and water reaction, the shortcoming of this method is, have by-product 4-hydroxybutyrate ethyl ester etc. generation, and the use of red phosphorus and bromine is potentially dangerous and the post-treatment process is complicated, especially the purity is not high, it is not suitable for large-scale industrial production, and cannot meet the needs of high-purity products

Yet the shortcoming of this method is: owing to be to pass into hydrogen bromide gas in the mixture of gamma-butyrolactone and dehydrated alcohol, there will be the side reaction that hydrogen bromide and ethanol generate bromoethane to take place, and used ethanol is Absolute ethanol is used in a large amount, which leads to the waste of raw material hydrogen bromide gas and ethanol. The reaction time is too long. It needs to be extracted with ethyl bromide during post-treatment. The production process requires vacuum distillation equipment. The operation is complicated and the production cost is high and the yield is high. and purity are low, unable to meet the demand for high-purity products

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