Synthesis method of benzyloxyamine hydrochloride

Abstract

The present invention provides a benzyloxyamine hydrochloride synthesis method, which comprises: carrying out an alkylation reaction on a hydroxylamine compound and a benzyl halide under an alkaline condition to prepare a benzyl compound crude product, and refining the benzyl compound crude product to prepare a finished product, the alkylation reaction comprises the following steps: S11, preparing the hydroxylamine compound and the benzyl halide, dividing the benzyl halide into two parts; s12, under the reaction temperature condition of 25-30 DEG C, one part of benzyl halide is dropwise added into the hydroxylamine compound solution, and after dropwise adding is completed, the reaction is completed under the constant-temperature condition; and S13, under the reaction temperature condition of 35-40 DEG C, dropwise adding the rest part of benzyl halide into the hydroxylamine compound solution, after dropwise adding is completed, under the constant-temperature condition until the reaction is complete, and after sampling and detecting that no benzyl halide exists, completing the alkylation reaction. The invention aims to provide a synthesis method of benzyloxyamine hydrochloride, which can reduce the generation of byproducts in an alkylation step and is used for preparing benzyloxyamine hydrochloride with higher purity.

Description

technical field [0001] The present invention relates to the technical field of organic synthesis, in particular to a synthetic method of benzyloxyamine hydrochloride. Background technique [0002] Benzyloxyamine hydrochloride is an important medicine and an intermediate used in the synthesis of herbicides, and the purity requirement is particularly high in the process of being applied to medicine synthesis. One is its application in the synthesis of new anticancer drugs as an example. The purity of benzyloxyamine hydrochloride must meet the following requirements: the content measured by potentiometric titration is more than 98%, and the content measured by gas chromatography is more than 99%. And the content measured by liquid chromatography is 98% or more. [0003] At present, the preparation method of benzyloxyamine hydrochloride that can realize industrialized production includes following three kinds: [0004] 1. The ketoxime ether method represented by the Chinese in...

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Problems solved by technology

[0007] The above three methods all adopt benzyl chloride or benzyl bromide as the alkylation reagent, the alkylation reaction process, the hydrolysis process, the separation of crude product benzyloxyamine, refining and drying, etc., but the produced by these three methods The purity of benzyloxyamine hydrochloride is relatively low and cannot meet the quality requirement of more than 98%.

[0008] In the method for synthesizing benzyloxyamine hydrochloride (CN102531950A) invented by Shandong Aodong Chemical Zhang Zhen, etc., after the alkylation reaction is completed, an aqueous solution of liquid alkali is used to remove excess benzyl chloride and increase the content of the product by potentiometric titration. (more than 98% by potentiometric titration), but the liquid chromatographic content is only 91%, and the gas chromatographic content is about 95%, which does not meet the relevant requirements for use.