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A kind of preparation method of 2-amino-4-bromo-3-fluoro-5-iodobenzamide

A technology of iodobenzamide and amino group, which is applied in the preparation of carboxylic acid amides, nitro compounds, organic compounds, etc., can solve the problem of low yield of iodobenzamide, 2-fluoro-3-bromonitrobenzene Expensive, unfavorable industrial scale-up and other problems, to achieve the effect of high yield and low cost

Active Publication Date: 2022-03-11
无锡双启科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] In the above synthetic method, in the process of synthesizing 2-amino-4-bromo-3-fluoro-5-iodobenzamide compound I, the price of starting material 2-fluoro-3-bromonitrobenzene is very expensive, and the last step The reaction is condensed with a condensing agent to produce 2-amino-4-bromo-3-fluoro-5-iodobenzamide. The yield is low, and it needs to be purified by a column method, which is not conducive to industrial scale-up.

Method used

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  • A kind of preparation method of 2-amino-4-bromo-3-fluoro-5-iodobenzamide
  • A kind of preparation method of 2-amino-4-bromo-3-fluoro-5-iodobenzamide
  • A kind of preparation method of 2-amino-4-bromo-3-fluoro-5-iodobenzamide

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Embodiment 1

[0031] A preparation method of 2-amino-4-bromo-3-fluoro-5-iodobenzamide, said preparation method comprising the steps of:

[0032] (1) Synthesis of compound III

[0033] Add 193g (1mol) 2,3-difluorobromobenzene and 1000ml tetrahydrofuran to the reaction flask, drop the temperature to -78°C and add 500ml 2.5M butyllithium dropwise, stir for 30min after dropping, pass carbon dioxide, and keep the temperature for 1 hour. HPLC followed the reaction until the reaction of 2,3-difluorobromobenzene was complete; 1000ml of water was added to quench the reaction, 1000ml of ethyl acetate was layered, the aqueous layer was acidified to PH=3, and a solid was precipitated, which was filtered and dried to obtain 222g of compound III. Molar yield: 93.6%.

[0034] (2) Synthesis of compound IV

[0035] Add 200g (843.9mmol) of compound III and 1000ml of 98% concentrated sulfuric acid to the reaction flask, drop the temperature to 0°C and add 118.7g (1266mmol) of 68% concentrated nitric acid dr...

Embodiment 2

[0049] A preparation method of 2-amino-4-bromo-3-fluoro-5-iodobenzamide, said preparation method comprising the steps of:

[0050] (1) Synthesis of compound III

[0051] Add 193g (1mol) 2,3-difluorobromobenzene and 1000ml tetrahydrofuran to the reaction flask, drop the temperature to -78°C, add 400ml 2.5M butyl lithium dropwise, stir for 30min after dropping, pass carbon dioxide, and keep the temperature for 2 hours. HPLC followed the reaction until the reaction of 2,3-difluorobromobenzene was complete; 1000ml of water was added to quench the reaction, 1000ml of ethyl acetate was layered, the aqueous layer was acidified to PH=3, a solid was precipitated, and 201.8g of compound III was obtained by filtration and drying , Molar yield: 85.1%.

[0052] (2) Synthesis of Compound IV

[0053] Add 200g (843.9mmol) of compound III and 1000ml of concentrated sulfuric acid to the reaction flask, drop the temperature to 30°C and add 98.9g (1055mmol) of 68% concentrated nitric acid dropwis...

Embodiment 3

[0065] A preparation method of 2-amino-4-bromo-3-fluoro-5-iodobenzamide, said preparation method comprising the steps of:

[0066] (1) Synthesis of compound III

[0067] Add 193g (1mol) 2,3-difluorobromobenzene and 1000ml tetrahydrofuran to the reaction flask, drop the temperature to -78°C, add 440ml 2.5M butyl lithium dropwise, stir for 30min after dropping, pass carbon dioxide, and keep the temperature for 1.5 hours. HPLC followed the reaction until the reaction of 2,3-difluorobromobenzene was complete; 1000ml of water was added to quench the reaction, 1000ml of ethyl acetate was layered, the aqueous layer was acidified to PH=3, a solid was precipitated, filtered and dried to obtain 211.4g of compound III , Molar yield: 89.1%.

[0068] (2) Synthesis of compound IV

[0069] Add 200g (843.9mmol) of compound III and 1000ml of concentrated sulfuric acid to the reaction flask, drop the temperature to 15°C and add 79.2g (843.9mmol) of 68% concentrated nitric acid dropwise, slowl...

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Abstract

The invention discloses a preparation method of 2-amino-4-bromo-3-fluoro-5-iodobenzamide, the preparation method comprising the following steps: (1) compound (II) is extracted from butyllithium Under conditions, pass carbon dioxide, generate compound (III); (2) compound (III) generates compound (IV) through concentrated sulfuric acid, nitric acid nitration; (3) compound (IV) reacts with acid chloride to generate compound (V); (4) Compound (V) reacts with ammonia water to generate amide compound (VI); (5) amide compound (VI) obtains compound (VII) through iron powder reduction; (6) compound (VII) obtains compound (VII) through Sandmeyer reaction VIII); (7) compound (VIII) generates compound (I) through ammonia gas high-pressure reaction. The production rate of the preparation method of the present invention is higher.

Description

technical field [0001] The invention relates to the technical field of medicine and chemical industry, in particular to a preparation method of 2-amino-4-bromo-3-fluoro-5-iodobenzamide. Background technique [0002] 2-Amino-4-bromo-3-fluoro-5-iodobenzamide is a key intermediate, and WO2018143315 and US20180015087 disclose the following synthesis of 2-amino-4-bromo-3-fluoro-5-iodobenzamide The route of compound I: [0003] [0004] In the above synthetic method, in the process of synthesizing 2-amino-4-bromo-3-fluoro-5-iodobenzamide compound I, the price of starting material 2-fluoro-3-bromonitrobenzene is very expensive, and the last step The reaction uses a condensing agent to condense to produce 2-amino-4-bromo-3-fluoro-5-iodobenzamide with a low yield and requires column purification, which is not conducive to industrial scale-up. Contents of the invention [0005] In view of the above problems in the prior art, the applicant of the present invention provides a pre...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C231/12C07C237/30
CPCC07C231/12C07C231/02C07C201/12C07C201/08C07C51/15C07C237/30C07C233/65C07C205/58C07C63/70
Inventor 张国强
Owner 无锡双启科技有限公司
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