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Preparation method of 2-amino-4'-fluoro-diphenyl ketone

A technology of benzophenone and amino group is applied in the field of preparation of 2-amino-4'-fluoro-benzophenone, can solve the problems of difficulty in industrialization, many reagents, complicated operation and the like, and achieves obvious cost advantages and convenient operation. Controllable, easy-to-use effects

Active Publication Date: 2018-02-09
ANHUI QINGYUN PHARMA & CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Route 1, using o-nitrobenzoic acid as the starting material, the product is obtained through acid chloride reaction, Friedel-Crafts acylation, and reduction. Although the route is relatively short, the acid chloride reaction uses sulfuryl chloride to produce polluting by-products, etc. There are environmental protection problems in the industrial scale-up of this reaction; on the other hand, the raw material cost of this route is relatively high, and it is difficult to realize large-scale industrialization;
[0005] Route 2, using phthalic anhydride as the starting material, first performs Friedel-Crafts acylation reaction with fluorobenzene to obtain p-fluorobenzoylbenzoic acid, and then undergoes acid chloride reaction, amidation reaction, and Hofmann degradation to obtain 2- Amino-4'-fluoro-benzophenone, although the yield of each step of this reaction is high, the reagents used are many and the route is long, which is not conducive to industrial production;
[0006] Route 3, using anisole as a raw material, first protect the amino group with p-toluenesulfonyl chloride, then acyl chloride to obtain acid chloride, and then perform Friedel-Crafts reaction with fluorobenzene to obtain 2-amino-4'-fluoro-benzophenone Ketones, the route is long and the overall yield is low
[0007] It can be seen that the current synthetic route of 2-amino-4'-fluoro-benzophenone is either because of the high cost of raw materials, or because of the long route and complicated operation, or because of the shortcomings of low yield and large environmental pollution. Difficulties in industrialization

Method used

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  • Preparation method of 2-amino-4'-fluoro-diphenyl ketone

Examples

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Embodiment 1

[0039] A preparation method of 2-amino-4'-fluoro-benzophenone, comprising the following steps: o-nitrotoluene is chlorinated by chlorine gas to obtain o-nitrobenzotrichlorotoluene; and then reacted with fluorobenzene by Friedel-Crafts-hydrolysis to obtain 2-nitro-4'-fluoro-benzophenone; and then reduced to 2-amino-4'-fluoro-benzophenone.

Embodiment 2

[0041] A preparation method of 2-amino-4'-fluoro-benzophenone, comprising the following steps: take o-nitrotoluene, heat up to 48°C, pass chlorine gas for 2 hours, heat up to 105°C, continue to pass chlorine gas for 6 hours, cool To room temperature to obtain o-nitrobenzotrichloride, wherein the molar ratio of o-nitrotoluene and chlorine is 1:3.5;

[0042] Mix fluorobenzene and aluminum trichloride evenly, cool down to 10°C, add o-nitrotrichlorotoluene dropwise, keep stirring for 40 minutes after the dropwise addition, then adjust the temperature to room temperature, keep it warm for 5 hours, then cool down to 2°C, add water dropwise , and then heated to 100°C, kept warm for 1.5h, cooled to room temperature to crystallize, filtered, and recrystallized with methanol to obtain 2-nitro-4'-fluoro-benzophenone, wherein the moles of fluorobenzene and aluminum trichloride The ratio is 1:3, and the weight ratio of fluorobenzene and water is 1:4;

[0043] Mix 2-nitro-4'-fluoro-benzoph...

Embodiment 3

[0045] A preparation method of 2-amino-4'-fluoro-benzophenone, comprising the following steps: take o-nitrotoluene, heat up to 42°C, pass chlorine gas for 2 hours, then heat up to 115°C, continue to pass chlorine gas for 4.5 hours, Cool to room temperature to obtain o-nitrobenzotrichloride, wherein the molar ratio of o-nitrotoluene and chlorine is 1:4.5;

[0046] Mix fluorobenzene and aluminum trichloride evenly, cool down to 0°C, add o-nitrotrichlorotoluene dropwise, keep stirring for 60 minutes after the dropwise addition, then adjust the temperature to room temperature, keep it warm for 2 hours, then cool down to 5°C, add water dropwise , then heated to 40°C, kept warm for 4h, cooled to room temperature for crystallization, filtered, and recrystallized with methanol to obtain 2-nitro-4'-fluoro-benzophenone, wherein the molar ratio of fluorobenzene to aluminum trichloride 1:1.2, the weight ratio of fluorobenzene and water is 1:10;

[0047] Mix 2-nitro-4'-fluoro-benzophenone...

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Abstract

The invention discloses a preparation method of 2-amino-4'-fluoro-diphenyl ketone. The preparation method comprises the following steps that ortho-nitrotoluene is chloridized by chlorine gas to obtainO-nitrotrichlorotoluene; then the O-nitrotrichlorotoluene performs Fridel-Crafts hydrolysis reaction with fluorobenzene to obtain 2-nitryl-4'-fluoro-diphenyl ketone; the 2-amino-4'-fluoro-diphenyl ketone is obtained through reduction. The synthetic route of the method is green and friend to the environment, the yield is high, the prepared 2-amino-4'-fluoro-diphenyl ketone is high in purity, the starting raw materials are cheap and easy to obtain, and the method is low in cost, easy to operate and suitable for industrial production.

Description

technical field [0001] The invention relates to the technical field of chemical substance preparation, in particular to a preparation method of 2-amino-4'-fluoro-benzophenone. Background technique [0002] Pitavastatin calcium is the third-generation statin drug, and it is one of the statin drugs with better blood lipid-lowering effect in international clinical application. It has the characteristics of high efficiency, safety, and good tolerance. 2-Amino-4'-fluoro-benzophenone is a key intermediate used in the production of pitavastatin calcium. [0003] At present, the synthetic routes of 2-amino-4'-fluoro-benzophenone mainly contain the following methods: [0004] Route 1, using o-nitrobenzoic acid as the starting material, the product is obtained through acid chloride reaction, Friedel-Crafts acylation, and reduction. Although the route is relatively short, the acid chloride reaction uses sulfuryl chloride to produce polluting by-products, etc. There are environmental ...

Claims

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Application Information

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IPC IPC(8): C07C221/00C07C225/22C07C201/12C07C205/11C07C205/45
CPCC07C201/12C07C221/00C07C225/22C07C205/45C07C205/11
Inventor 黄欢黄庆国李凯
Owner ANHUI QINGYUN PHARMA & CHEM
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