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A method for synthesizing 5-chloro-2-methyl-4-(trifluoromethyl)aniline in one step

A trifluoromethyl, synthesis method technology, applied in the direction of preparation of amino compounds from amines, purification/separation of amino compounds, organic chemistry, etc., to achieve the effects of high yield, reasonable design, and simple operation

Active Publication Date: 2022-05-13
阿里生物新材料(常州)有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the synthesis method of 5-chloro-2-methyl-4-(trifluoromethyl)aniline is rarely reported in the literature

Method used

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Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0018] A method for synthesizing 5-chloro-2-methyl-4-(trifluoromethyl)aniline in one step, the synthesis method comprises the following steps: according to the mass ratio of compound A, compound B, catalyst and carbonate is 50~ 55:45~50:5~10:45~47, the solid-liquid g / mL ratio of compound A and dioxane is 1:30, the raw materials are taken, and then compound A, catalyst and dioxane are mixed under nitrogen protection Put oxyhexane into the reactor, stir for 5 minutes, then add compound B and carbonate, raise the temperature to 100-105°C, and stir for 15-20 hours to obtain compound C, which is 5-chloro-2-methyl- 4-(Trifluoromethyl)aniline.

[0019] The chemical reaction formula of this synthesis is as follows

[0020] .

Embodiment 1

[0022] The catalyst is Pd(Dppf)Cl 2 .

[0023] The carbonate is any one of sodium carbonate and potassium carbonate.

[0024] A method for synthesizing 5-chloro-2-methyl-4-(trifluoromethyl)aniline in one step, the synthetic method comprises the following steps: under nitrogen protection, 5g compound A, 0.5g catalyst and 150mL dioxane Put the ring into the reactor, stir for 5min, then add 4.5g of compound B and 4.5g of carbonate, heat up to 100°C, stir and react for 15h, HPLC detects that the reaction of the raw materials is complete, the reaction solution is filtered through diatomaceous earth, concentrated, and the sample is mixed , 2.8 g of brown oil was obtained by passing through the column, that is, compound C, namely 5-chloro-2-methyl-4-(trifluoromethyl)aniline, with a yield of 85.9% and a purity of 99.1%.

[0025] The chemical reaction formula of this synthesis is as follows

[0026] .

[0027] NMR of 5-chloro-2-methyl-4-(trifluoromethyl)aniline: 1H NMR (d6-DMSO):...

Embodiment 2

[0029] The catalyst is Pd(Dppf)Cl 2 .

[0030] The carbonate is any one of sodium carbonate and potassium carbonate.

[0031] A method for synthesizing 5-chloro-2-methyl-4-(trifluoromethyl)aniline in one step, the synthetic method comprises the following steps: under nitrogen protection, 5g compound A, 0.8g catalyst and 150mL dioxane Put the ring into the reactor, stir for 5min, then add 4.8g of compound B and 4.6g of carbonate, heat up to 103°C, stir and react for 17h, HPLC detects that the reaction of the raw materials is complete, the reaction solution is filtered through diatomaceous earth, concentrated, and the sample is mixed , 3 g of brown oil was obtained by passing through the column, that is, compound C, namely 5-chloro-2-methyl-4-(trifluoromethyl)aniline, with a yield of 92.0% and a purity of 99.6%.

[0032] The chemical reaction formula of this synthesis is as follows

[0033] .

[0034] NMR of 5-chloro-2-methyl-4-(trifluoromethyl)aniline: 1H NMR (d6-DMSO): 7...

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Abstract

The invention belongs to the technical field of pharmaceutical intermediates, in particular to a method for synthesizing 5-chloro-2-methyl-4-(trifluoromethyl)aniline in one step. The present invention provides a one-step method for synthesizing 5-chloro-2-methyl-4-(trifluoromethyl)aniline for the first time, using compound A as a starting material, catalyzed by a catalyst, reacting with compound B, and directly synthesizing product 5 in one step -Chloro-2-methyl-4-(trifluoromethyl)aniline, and use carbonate to eliminate the generated acid, which improves the yield and purity.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical intermediates, and specifically relates to a method for synthesizing 5-chloro-2-methyl-4-(trifluoromethyl)aniline in one step. Background technique [0002] The compound 5-chloro-2-methyl-4-(trifluoromethyl)aniline and related derivatives are widely used in medicinal chemistry and organic synthesis. Currently, there are few reports on the synthesis of 5-chloro-2-methyl-4-(trifluoromethyl)aniline. Therefore, it is necessary to develop a synthetic method that is easy to obtain raw materials, easy to operate, easy to control the reaction, suitable for overall yield, and suitable for industrial production. Contents of the invention [0003] Technical problem to be solved by the present invention: Aiming at the problems mentioned above, a method for synthesizing 5-chloro-2-methyl-4-(trifluoromethyl)aniline in one step is provided. [0004] In order to solve the problems of the technologies d...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C209/68C07C209/84C07C211/52
CPCC07C209/68C07C209/84C07C211/52
Inventor 许义波戴红升刘超
Owner 阿里生物新材料(常州)有限公司