Preparation of medicament intermediate 1-methyl-3-phenyl piperazine

Abstract

The invention relates to a method for preparing a medicine intermediate, namely 1-methyl-3-phenyl-piperazine. Epoxy phenylethane and N-methyl ethanolamine react for ring opening in a methylbenzene solution and further react with thionyl chloride to obtain N-(2- chloroethyl)-N-methyl-2-chloro-2-phenylethylamine hydrochloride, the hydrochloride reacts with toluene sulfonamide and sodium hydroxide in a DMF solution to obtain 1-methyl-4-p-toluenesufonyl-3-phenylpiperazine, the 1-methyl-4-p-toluenesufonyl-3-phenylpiperazine reacts with concentrated hydrochloric acid to remove sulfonyl, and a product is obtained through neutralization extraction and recrystallization. Compared with the prior art, the method for preparing the 1-methyl-3-phenyl-piperazine has the advantages of low cost of selected raw materials, cost conservation, few synthesis steps, convenient and safe operation, simple post-treatment, high reaction yield, high product purity, good quality, and suitability for industrialized application.

Description

technical field The invention relates to a pharmaceutical intermediate, in particular to a preparation method of a pharmaceutical intermediate 1-methyl-3-phenylpiperazine. Background technique 1-methyl-3-phenylpiperazine (hereinafter referred to as MPP) is a key intermediate for the preparation of mirtazapine. Mirtazapine (mirtazapine) is an antidepressant drug (U.S.4062848). It is a selective serotonin reuptake inhibitor (SSRI). Clinical use in many countries of the world. So far, the methods for preparing MPP mainly contain the following: 1. Maeda, C.JP2001122863 reported that phenylglyoxal was used as a raw material, aminated and reduced to obtain 2-phenylpiperazine, and then methylated to obtain MPP. The synthetic route of this method is as follows: The raw materials used in this route are expensive, and the reaction yield is low, especially in the last step of methylation, there are several possible by-products, the yield is low, and it is not easy to purify. 2....

AI Technical Summary

Problems solved by technology

The design idea of ​​this method can be used for reference, but the flammable and explosive NaH and ether are used, and the yield is too low, the two-step yield is only 58.1%

Images