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N-(3-methyl chlorine) piperidine refining method

A purification method and chloropropyl technology, applied in the direction of organic chemistry and the like, can solve the problem that other impurities cannot be effectively removed from N-(3-chloropropyl) piperidine, and the content of N-(3-chloropropyl) piperidine is low. , the problem of unsatisfactory dehydration effect, etc., to achieve the effect of convenient industrial application, simple method and easy operation

Active Publication Date: 2015-03-11
河南豫辰药业股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, at present, most enterprises only dry N-(3-chloropropyl)piperidine with sodium sulfate (anhydrous sodium sulfate). This method cannot effectively remove N-(3-chloropropyl)piperidine. Other impurities in the crude product and low levels of N-(3-chloropropyl)piperidine
More importantly, the dehydration effect of this method is very unsatisfactory, and the obtained N-(3-chloropropyl)piperidine still contains 0.1%~1% moisture, which is used for the preparation of difenidol hydrochloride by Grignard reaction The effect is very unsatisfactory

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Add 20 g of crude N-(3-chloropropyl)piperidine and 5 g of anhydrous sodium sulfate into a round bottom flask, stir overnight, then transfer the above mixture and zeolite into a distillation flask, and control the distillation device with a rotary vane vacuum pump The vacuum degree is 300Pa~400Pa, and the low boiling point substances with boiling point≤90℃, high boiling point substances with boiling point≥120℃, positive boiling point substances with 90℃<boiling point<120℃ and positive boiling point substances with 90℃<boiling point<120℃ are respectively collected. The substance is the obtained fine N-(3-chloropropyl)piperidine, its water content is ≤0.05%, and the content of N-(3-chloropropyl)piperidine is ≥99.2%.

Embodiment 2

[0018] Add 20 g of crude N-(3-chloropropyl)piperidine and 4 g of anhydrous magnesium sulfate into a round bottom flask, stir overnight, then transfer the above mixture and zeolite into a distillation flask, and use a rotary vane vacuum pump to control the distillation device The vacuum degree is 300Pa~400Pa, and the low boiling point substances with boiling point≤90℃, high boiling point substances with boiling point≥120℃, positive boiling point substances with 90℃<boiling point<120℃ and positive boiling point substances with 90℃<boiling point<120℃ are respectively collected. The substance is the obtained N-(3-chloropropyl)piperidine fine product, its water content is ≤0.04%, and the content of N-(3-chloropropyl)piperidine is ≥99.2%.

Embodiment 3

[0020] Add 20 g of crude N-(3-chloropropyl)piperidine and 5 g of anhydrous calcium chloride into a round bottom flask, stir overnight, then transfer the above mixture and zeolite into a distillation flask, and use a rotary vane vacuum pump to control the distillation The vacuum degree of the device is 300Pa~400Pa, and the low boiling point substances with boiling point ≤90°C, high boiling point substances with boiling point ≥120°C, positive boiling point substances with 90°C<boiling point<120°C, and positive The boiling point substance is the obtained N-(3-chloropropyl)piperidine fine product, its water content is ≤0.05%, and the content of N-(3-chloropropyl)piperidine is ≥99.2%.

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Abstract

The invention discloses an N-(3-methyl chlorine) piperidine refining method which comprises the following steps: drying an N-(3-methyl chlorine) piperidine crude product for one night by using an alkaline or neutral desiccant, then carrying out heating and high-vacuum distillation on the dried crude product, removing impurities with low boiling points and high boiling points, collecting fractions within a required temperature range and obtaining an N-(3-methyl chlorine) piperidine fine product. The N-(3-methyl chlorine) piperidine refining method has the benefits that moisture and other impurities in the N-(3-methyl chlorine) piperidine crude product can be efficiently removed, so that the refined fine produced can be safely and effectively subjected to Grignard reaction; moreover, the method has the advantages of high simplicity, high simplicity and convenience in operation and low cost and is suitable for being used in pharmaceutical enterprises.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, in particular to a method for refining a drug intermediate, in particular to a method for refining N-(3-chloropropyl)piperidine. Background technique [0002] N-(3-chloropropyl)piperidine is an important intermediate in the synthesis of diphenidol hydrochloride for vertigo withdrawal, and the Grignard reaction using this substance as a raw material is an important reaction for the synthesis of difenidol hydrochloride. Wherein, the Grignard reagent used in the Grignard reaction is an organomagnesium compound, which is an alkylmagnesium halide RMgX generated by the reaction of a halogenated hydrocarbon with metal magnesium in anhydrous ether or THF. Grignard reagents are particularly sensitive to water, because water contains active protons, which can react with Grignard reagents to cause hydrolysis, resulting in the failure of Grignard reagents. Therefore, when carrying out Grignard r...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D211/06
CPCC07D295/067
Inventor 魏利强石艳彩王利叶唐松涛
Owner 河南豫辰药业股份有限公司