Continuous flow preparation method of 4 '-fluoro-2-phenyl acetophenone

A technology of phenylacetophenone and fluorobenzene is applied in the field of pharmaceutical synthesis technology, and can solve the problems of corrosion of reaction equipment, harm to human body, generation of impurities, etc., and achieve the effect of reducing defluorination impurities and improving product quality.

Pending Publication Date: 2022-03-25
河南豫辰药业股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

These two preparation methods will cause impurities, and use dangerous chemicals phenylacetyl chloride, anhydrous AlCl 3 , fluorobenzene, etc., will cause harm to the human body, an...

Method used

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  • Continuous flow preparation method of 4 '-fluoro-2-phenyl acetophenone
  • Continuous flow preparation method of 4 '-fluoro-2-phenyl acetophenone
  • Continuous flow preparation method of 4 '-fluoro-2-phenyl acetophenone

Examples

Experimental program
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Effect test

Embodiment 1

[0049] The present invention adopts continuous flow reaction system to carry out continuous preparation of 4'-fluoro-2-phenylacetophenone, such as Figure 1-3 As shown, the continuous flow reaction system includes a first raw material storage tank 1, a second raw material storage tank 2, a T-shaped gradient mixer 3, a coil microreactor 4, and a product collection tank 5;

[0050] The first raw material storage tank 1 is used for storing phenylacetyl chloride, aluminum trichloride and organic solvent I, and the second raw material storage tank 2 is used for storing fluorobenzene and organic solvent II.

[0051] Such as Figure 2-3 As shown, the T-shaped gradient mixer 3 is a cylindrical structure made of polytetrafluoroethylene, with a diameter of 8 cm, a wall thickness of 1-1.5 cm, and a body height of 20 cm, including a reactor body 31 and a top cover arranged on the top of the reactor body 31 32. The top cover 32 is detachably connected to the side wall of the reactor body ...

Embodiment 2

[0063] A continuous flow preparation method of 4'-fluoro-2-phenylacetophenone, using the continuous flow reaction system in Example 1 to continuously prepare 4'-fluoro-2-phenylacetophenone, the specific steps are as follows ;

[0064] (1) Continuously prepare material A solution in the first raw material storage tank 1: Dissolve aluminum trichloride (16.001 g, 0.12 mol) and phenylacetyl chloride (15.459 g, 0.1 mol) in 300 mL of trichloro methane, and in the first raw material storage tank 1, the temperature of the material A solution is maintained at 10°C to 20°C through heat exchange equipment;

[0065] (2) Continuously prepare material B solution in the second raw material storage tank 2: Dissolve fluorobenzene (10.572 g, 0.11 mol) in 200 mL chloroform under stirring conditions, and pass through the second raw material storage tank 2 Heat exchange equipment keeps the temperature of material B solution at 10°C~20°C;

[0066] (3) Start the first feed pump and the second feed...

Embodiment 3

[0070] A continuous flow preparation method of 4'-fluoro-2-phenylacetophenone, using the continuous flow reaction system in Example 1 to continuously prepare 4'-fluoro-2-phenylacetophenone, the specific steps are as follows ;

[0071] (1) Continuously prepare material A solution in the first raw material storage tank 1: Dissolve aluminum trichloride (16.001 g, 0.12 mol) and phenylacetyl chloride (15.459 g, 0.1 mol) in 300 mL of trichloro methane, and in the first raw material storage tank 1, the temperature of the material A solution is maintained at 10°C to 20°C through heat exchange equipment;

[0072] (2) Continuously prepare material B solution in the second raw material storage tank 2: Dissolve fluorobenzene (10.572 g, 0.11 mol) in 200 mL chloroform under stirring conditions, and pass through the second raw material storage tank 2 Heat exchange equipment keeps the temperature of material B solution at 10°C~20°C;

[0073](3) Start the first feed pump and the second feed ...

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Abstract

The invention belongs to the technical field of medicine synthesis processes, and particularly relates to a continuous flow preparation method of 4 '-fluoro-2-phenyl acetophenone. According to the method, AlCl3 is dissolved in phenylacetyl chloride, and phenylacetyl chloride and fluorobenzene are subjected to instantaneous mixing reaction, so that fluorine impurities are reduced, the product quality is improved, and the whole preparation process is continuous from material preparation to material mixing to reaction completion. The continuous flow reaction system is used for continuously preparing 4 '-fluoro-2-phenylacetophenone, the preparation conditions are mild, the reaction speed is fully increased, side reactions are reduced and prevented, the product quality is improved, the problem of unstable fluidity of solid slurry is solved, corrosion of acid gas to equipment can be avoided, the production efficiency is improved, and the production cost is reduced. The environmental pollution is reduced.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis technology, and in particular relates to a continuous flow preparation method of 4'-fluoro-2-phenylacetophenone. Background technique [0002] 4′-Fluoro-2-phenylacetophenone is the key intermediate of atorvastatin core. Generally, phenylacetyl chloride and fluorobenzene are used as raw materials, and anhydrous AlCl 3 The catalyst is obtained through Friedel-Crafts acylation reaction. [0003] In the prior art, the preparation method of 4'-fluoro-2-phenylacetophenone mainly contains two kinds: 1, select fluorobenzene to do reactant and solvent for use, in anhydrous AlCl 3 Adding phenylacetyl chloride dropwise under the condition of the catalyst, a large excess of fluorobenzene shifts the reaction equilibrium to the right, which improves the conversion rate of the acylating reagent and the selectivity of the product, but at the same time, the presence of a large amount of fluorobenzene w...

Claims

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Application Information

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IPC IPC(8): C07C45/46C07C49/813B01J19/00B01J19/24
CPCC07C45/46B01J19/0093B01J19/24B01J19/0053C07C49/813
Inventor 鞠志宇傅收石艳彩路明贾玉香刘玉层王燕旭马彦召周金龙
Owner 河南豫辰药业股份有限公司
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