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Preparation method of substituted phenylacetic acid derivative

A kind of derivative, the technology of phenylacetic acid, which is applied in the preparation of organic compounds, the preparation of carboxylate, the preparation of sulfonic acid amides, etc., can solve the problems of difficult purification, mandelic acid is easily soluble in water, and the synthesis route is short and the product quality is short. The effect of short process route, simple extraction and mild reaction conditions

Active Publication Date: 2015-09-09
ZHEJIANG APELOA JIAYUAN PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This route is a hotspot in the research of p-hydroxyphenylacetic acid. The synthesis route is short, the steps are simple, and the product quality is high. The disadvantage is that p-hydroxymandelic acid is easily soluble in water and difficult to purify.

Method used

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  • Preparation method of substituted phenylacetic acid derivative
  • Preparation method of substituted phenylacetic acid derivative
  • Preparation method of substituted phenylacetic acid derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049]

[0050]Add phenylglycine (181g, 1.2mol) into aqueous sodium hydroxide solution (2M, 1000mL, 2.0mol), start stirring, control the temperature at 0-10°C, add methanesulfonyl chloride (165g, 1.44mol) dropwise in dichloromethane (800mL), after the dropwise addition, stir until the reaction is complete, then separate layers to remove the organic phase, add hydrochloric acid dropwise to the water phase, adjust the pH value to 1-2, the solid precipitates, cool and stir, filter, and bake the filter cake Dry to obtain 264g of intermediate sulfonyl-protected phenylglycine. Dissolve the intermediate in dichloromethane (1000 mL), add methanesulfonic acid (28 g, 0.288 mol), then control the temperature at about 15-25 ° C, add sodium borohydride (22 g, 0.58 mol) in batches, and stir at room temperature until The reaction is complete. After the reaction is complete, add water (1000mL) and 40% liquid caustic soda (160g) to the reaction solution, stir the reaction, let stand to sepa...

Embodiment 2

[0052]

[0053] Add p-hydroxyphenylglycine (200g, 1.2mol) into aqueous sodium hydroxide solution (2M, 1000mL, 2.0mol), start stirring, control the temperature at 0-5°C, add p-toluenesulfonyl chloride (274g, 1.44mol) dropwise in Solution in dichloromethane (800mL), stir until the reaction is complete after the dropwise addition, then separate layers, remove the organic phase, add hydrochloric acid dropwise to the water phase, adjust the pH value to 1~2, solid precipitates, cool and stir, filter , and the filter cake was dried to obtain 366g of sulfonyl-protected p-hydroxyphenylglycine. Dissolve the intermediate in dichloromethane (1000 mL), add trifluoroacetic acid (26 g, 0.228 mol), then control the temperature at about 15-25 ° C, add sodium borohydride (26 g, 0.68 mol) in batches, and stir at room temperature until The reaction is complete. After the reaction is complete, add water (1000mL) and 40% liquid caustic soda (160g) to the reaction solution, stir the reaction, let...

Embodiment 3

[0056]

[0057] Add p-methoxyphenylglycine (217g, 1.2mol) into aqueous sodium hydroxide solution (2M, 1000mL, 2.0mol), start stirring, control the temperature at 0-10°C, add p-toluenesulfonyl chloride (274g, 1.44mol) dropwise ) solution in dichloromethane (800mL), stir until the reaction is complete after the dropwise addition is complete, then separate layers to remove the organic phase, add hydrochloric acid dropwise to the water phase, adjust the pH value to 1~2, solids are precipitated, cooled and stirred, Filter and dry the filter cake to obtain 362 g of sulfonyl-protected p-methoxyphenylglycine. Dissolve the intermediate in dichloromethane (1000 mL), add trifluoroacetic acid (37 g, 0.228 mol), then control the temperature at about 15-25 ° C, add sodium borohydride (20 g, 0.54 mol) in batches, and stir at room temperature until The reaction is complete. After the reaction is complete, add water (1000mL) and 40% liquid caustic soda (160g) to the reaction solution, let i...

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Abstract

The invention discloses a preparation method of a substituted phenylacetic acid derivative. The method comprises the following steps: 1, carrying out a sulfonylation reaction on substituted phenylglycine and sulfuryl chloride under the action of an alkali, and post-processing after completing the reaction to obtain an intermediate; and 2, carrying out a deamination reaction on the intermediate obtained in step 1 under the action of an organic acid and a reducing agent, and post-processing after completing the reaction to obtain the substituted phenylacetic acid derivative. The raw material phenylglycine used in the above route can be very easily purchased from the market, and is cheap and easily available. The preparation method has the advantages of short process route, mild reaction conditions, simple operation, high reaction yield and low total lost.

Description

technical field [0001] The invention relates to a preparation method of a pharmaceutical intermediate, in particular to a preparation method of a substituted phenylacetic acid derivative, belonging to the field of organic synthesis. Background technique [0002] Phenylacetic acid derivatives are important intermediates in organic synthesis, widely used in medicine, pesticides, dyes and other fields. [0003] The synthetic method of the currently disclosed phenylacetic acid derivatives has the following types: [0004] Phenylacetonitrile method: using phenylacetonitrile as a raw material, first modify the benzene ring to obtain the target structure, and then hydrolyze it to obtain p-hydroxyphenylacetic acid (Sheng Weicheng, Chinese Journal of Pharmaceutical Industry, 1993, 24(6): 276-277). The raw material of this method is easy to get, but the reaction route is long, the side reaction is obvious, and the reaction yield is low. [0005] Trichloroacetaldehyde method: use phe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C51/377C07C57/32C07C57/58C07C59/52C07C59/64C07C303/38C07C311/08
CPCC07C51/377C07C303/38C07C311/08C07C57/32C07C57/58C07C59/52C07C59/64
Inventor 刘伟军胡明阳毛志军吴丹红
Owner ZHEJIANG APELOA JIAYUAN PHARMA
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