A kind of preparation method of d(-)-α-(4-ethyl-2,3-dioxypiperazine-1-carboxamide) p-hydroxyphenylacetic acid

Abstract

The invention discloses a preparation method of D(-)-α-(4-ethyl-2,3-dioxypiperazine-1-carboxamido) p-hydroxyphenylacetic acid, which comprises 4-ethyl-2, The salt of 3-dioxopiperazine-1-formate and D-(-)-α-p-hydroxyphenylglycine undergoes a condensation reaction in the aqueous phase to obtain D(-)-α-(4-ethyl -2,3-Dioxypiperazine-1-carboxamido) p-hydroxyphenylacetic acid. The invention uses 4-ethyl-2,3-dioxopiperazine-1-methyl ester as a raw material, zinc halide as a catalyst, and adopts water phase reaction. Eliminate the use of organic solvents, improve the working environment, save post-processing costs, and greatly reduce the cost of "three wastes" treatment. The obtained HO-EPCP has high purity, and the purity of the one-step crystallization product is greater than 96%, without recrystallization, economical and The social benefits are remarkable.

Description

Technical field [0001] The present invention involves a preparation method of an intermediate of synthetic cephalosporone (pioneer) and sodium in the sodium in the sodium.-1-metharide) preparation method for hydroxybenzene (hereinafter referred to as HO-EPCP) is an organic synthetic technology field. Background technique [0002] Cefeius is a representative of the third -generation cephalosporin antibiotics. Flowing spectrum antibacterial is a first -line drug of anticurpal bacteria. It has received much attention in the antibiotic market. It has a huge market internationally and domestic.The abuse of antibiotics in policies has greatly increased the demand for cephalosporidone, which has become the top cephalosporin antibiotic in the market.HO-EPCP, as an important intermediate of the production of cephalosporone and 哌raxin, has shown considerable market potential.There are many reports about HO-EPCP synthesis literature, such as CN101508679B, CN1446807A, JP59036668A, DE21519400...

AI Technical Summary

Problems solved by technology

[0004] There are many problems in the above route: 1. Using a large amount of triphosgene and trimethylchlorosilane as raw materials, the intermediate EOCP is easy to hydrolyze, and requires a strict anhydrous operating environment; 2. EOCP is unstable and highly active, so the reaction needs to be carried out at low temperature ; 3. EOCP is difficult to separate and extract. Generally, the dichloromethane reaction liquid of EOCP is directly subjected to the next condensation reaction, which leads to an increase in by-products and increases the corresponding equipment and power facilities for post-processing.

4. A large amount of trimethylchlorosilane is used in the reaction, resulting in a large amount of silicon wastewater, and the cost of three wastes is high.

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