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Preparation method of 4-chloro-2-(trifluoroacetyl) aniline hydrochloride hydrate

A technology of trifluoroacetylphenyl and trifluoroacetyl, which is applied in the field of compound preparation, can solve the problems of difficult treatment and high cost, and achieve the effects of reducing the emission of "three wastes", low cost and simple operation

Inactive Publication Date: 2016-07-27
SHAXING CHEM TAIZHOU CITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The synthetic method of efavirenz has been reported in literature before: literature Tetrahedron, 1991,3207; J.Org.chem.63 (23), 1998,8536-8543; US5932726; US05925789; 4-chloro- A preparation method for 2-(trifluoroacetyl)aniline hydrochloride hydrate, but acetic acid is used in the reaction, resulting in many "three wastes" and difficult to handle; although the preparation method reported by CN102675125B does not use acetic acid, but Methyl or ethyl trifluoropyruvate is used in its reaction, and its cost is high

Method used

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  • Preparation method of 4-chloro-2-(trifluoroacetyl) aniline hydrochloride hydrate
  • Preparation method of 4-chloro-2-(trifluoroacetyl) aniline hydrochloride hydrate
  • Preparation method of 4-chloro-2-(trifluoroacetyl) aniline hydrochloride hydrate

Examples

Experimental program
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Effect test

Embodiment 1

[0018] ① React p-chloroaniline with pivaloyl chloride to obtain 4-chloro-N-pivaloyl anilide: put 40.2g p-chloroaniline and 250mL toluene into the reactor, cool down to 0-5°C, add 30% sodium hydroxide Solution 45.4g, control the temperature at 5-15°C, add 41.6g of pivaloyl chloride dropwise, drop over 1 hour, then keep warm at 5-15°C for 1 hour, separate layers, wash the organic layer twice, cool to -5°C, Keep warm for 2 hours, filter with suction, wash the filter cake with water, drain it, and dry the filter cake under vacuum at 70°C for 24 hours to obtain 64.5 g of 4-chloro-N-pivalanilide with a content of 99.4% and a yield of 96.8%.

[0019] ② 4-Chloro-N-pivalanilide reacts with ethyl trifluoroacetate under the action of butyllithium to obtain N-(4-chloro-2 trifluoroacetylphenyl)-pivalanamide: in the reactor Add 52.9g of 4-chloro-N-pivalanilide, 500mL of methyl tert-butyl ether, 29g of tetramethylethylenediamine, stir, cool to -20°C, and dropwise add butyllithium hexane with...

Embodiment 2

[0022] ① React p-chloroaniline with pivaloyl chloride to obtain 4-chloro-N-pivaloyl anilide: put 40.2g p-chloroaniline and 250mL toluene into the reactor, cool down to 0-5°C, add 30% sodium hydroxide Solution 45.4g, control the temperature at 5-15°C, add 41.6g of pivaloyl chloride dropwise, drop over 1 hour, then keep warm at 5-15°C for 1 hour, separate layers, wash the organic layer twice, cool to -5°C, Keep warm for 2 hours, filter with suction, wash the filter cake with water, drain it, and dry the filter cake under vacuum at 70°C for 24 hours to obtain 51.7 g of 4-chloro-N-pivalanilide, with a content of 99.4% and a yield of 96.8%.

[0023] ② 4-Chloro-N-pivalanilide reacts with ethyl trifluoroacetate under the action of butyllithium to obtain N-(4-chloro-2 trifluoroacetylphenyl)-pivalanamide: in the reactor Add 52.9g of 4-chloro-N-pivalanilide, 500mL of methyl tert-butyl ether, 29g of tetramethylethylenediamine, stir, cool to -20°C, and dropwise add butyllithium hexane wit...

Embodiment 3

[0026] ① React p-chloroaniline with pivaloyl chloride to obtain 4-chloro-N-pivaloyl anilide: put 40.2g p-chloroaniline and 250mL toluene into the reactor, cool down to 0-5°C, add 30% sodium hydroxide Solution 45.4g, control the temperature at 5-15°C, add 41.6g of pivaloyl chloride dropwise, drop over 1 hour, then keep warm at 5-15°C for 1 hour, separate layers, wash the organic layer twice, cool to -5°C, Keep warm for 2 hours, filter with suction, wash the filter cake with water, drain it, and dry the filter cake under vacuum at 70°C for 24 hours to obtain 51.7 g of 4-chloro-N-pivalanilide, with a content of 99.4% and a yield of 96.8%.

[0027] ② 4-Chloro-N-pivalanilide reacts with ethyl trifluoroacetate under the action of butyllithium to obtain N-(4-chloro-2 trifluoroacetylphenyl)-pivalanamide: in the reactor Add 52.9g of 4-chloro-N-pivalanilide, 500mL of methyl tert-butyl ether, 29g of tetramethylethylenediamine, stir, cool to -20°C, and dropwise add butyllithium hexane wit...

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Abstract

The invention discloses a preparation method of a 4-chloro-2-(trifluoroacetyl) aniline hydrochloride hydrate and belongs to the field of compound synthesis. The method adopts parachloroaniline as a raw material and comprises steps as follows: 1, parachloroaniline is subjected to a reaction with pivaloyl chloride, and 4-chloro-N-pivaloyl aniline is obtained; 2, 4-chloro-N-pivaloyl aniline is subjected to a reaction with ethyl trifluoroacetate under the action of n-butyllithium, and N-(4-chloro-2-trifluoroacetyl phenyl) pivaloyl amide is obtained; 3, N-(4-chloro-2-trifluoroacetyl phenyl) pivaloyl amide is subjected to a reaction with acid, pivaloyl is removed, and meanwhile, the 4-chloro-2-(trifluoroacetyl) aniline hydrochloride hydrate is obtained. The operation is simple, discharge of three wastes is greatly reduced, the treatment difficulty of the three wastes is reduced, the cost is low, the total recovery is up to 86.7%, and the preparation method of the 4-chloro-2-(trifluoroacetyl) aniline hydrochloride hydrate is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of compound preparation methods, in particular to a preparation method of 4-chloro-2-(trifluoroacetyl)aniline hydrochloride hydrate. Background technique [0002] 4-Chloro-2-(trifluoroacetyl)aniline hydrochloride hydrate is a key intermediate in the synthesis of anti-AIDS drug efavirenz. Efavirenz is a selective non-nucleoside reverse transcriptase inhibitor for human immunodeficiency virus (HIV-1). At the same time, efavirenz can be used in combination with other anti-HIV drugs to treat HVI-1 infection. First-line drugs for the treatment of AIDS. The synthetic method of efavirenz has been reported in literature before: literature Tetrahedron, 1991,3207; J.Org.chem.63 (23), 1998,8536-8543; US5932726; US05925789; 4-chloro- A preparation method for 2-(trifluoroacetyl)aniline hydrochloride hydrate, but acetic acid is used in the reaction, resulting in many "three wastes" and difficult to handle; although the preparatio...

Claims

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Application Information

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IPC IPC(8): C07C221/00C07C225/22
CPCC07C221/00C07C231/02C07C231/12C07C225/22C07C233/33C07C233/15
Inventor 王文秀吴金跃
Owner SHAXING CHEM TAIZHOU CITY
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