Preparation method of tetrahydropytanyl-4-formic acid and derivatives thereof by one-pot process

A technology of tetrahydropyran and derivatives, applied in organic chemistry and other fields, can solve the problems of expensive raw materials, complicated operation, cumbersome operation, etc., and achieve the effect of stable process, simple operation and improved overall yield

Inactive Publication Date: 2012-07-25
ASYMCHEM LAB TIANJIN +4
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] 1. Using tetrahydropyran-4-carboxylate, tetrahydropyran-4,4-dicarboxylic acid dimethyl ester, tetrahydropyran-4,4-dicarboxylic acid as starting materials, obtained by hydrolysis Tetrahydropyran-4-carboxylic acid and its derivatives, the raw material price of this method is expensive, and the operation is loaded down with trivial details;
[0005] 2. Using dichloroethyl ether as the initial raw material, reacting with sodium methoxide to close the ring, and then undergoing hydrolysis and decarboxylation to obtain tetrahydropyran-4-carboxylic acid and its derivatives, but the method has many steps, complicated operation, and low yield very low

Method used

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  • Preparation method of tetrahydropytanyl-4-formic acid and derivatives thereof by one-pot process
  • Preparation method of tetrahydropytanyl-4-formic acid and derivatives thereof by one-pot process
  • Preparation method of tetrahydropytanyl-4-formic acid and derivatives thereof by one-pot process

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Embodiment 1: A kind of one-pot method prepares tetrahydropyran-4-carboxylic acid The method is characterized in that the specific preparation steps are as follows:

[0028] (1) Ring closure: Add 417.6kg toluene (1g / 6mL), 172.5kg potassium carbonate (2.5eq) and 19.3kg tetrabutylammonium bromide (0.12eq) to a 1000L reactor in sequence, and heat up to 55±2°C , drop by 80.0kg diethyl malonate (1eq) and 93.0kg dichloroethyl ether (1:1.3eq) mixed solution, after dropping, keep warm at 50±2°C for 15h; after the reaction, cool the system down to 20-30°C, add 480kg of water (1g / 6mL) and 278.4kg of toluene (1g / 4mL) Extraction and liquid separation to obtain an organic phase;

[0029](2) Hydrolysis: Add 480kg (1g / 5mL) of 50% potassium hydroxide solution to the organic phase obtained in step (1), raise the temperature of the system to 80±2°C, keep it warm for 30h, and after the reaction is complete, cool the system to 20-30°C , add 160kg of water (1g / 2mL), separate the liquid...

Embodiment 2

[0031] Embodiment 2: A kind of one-pot method prepares 2,6-dimethyl-4-formic acid pyran The method is characterized in that the specific preparation steps are as follows:

[0032] (1) Ring closure: Add 277.4kg of ethylbenzene (1g / 1mL) to a 3000L reactor, start stirring, then add 424.0kg of anhydrous sodium carbonate (1:2.0eq) and 73.9kg of tetrabutylammonium iodide ( 1:0.05eq), warming up to 63±2°C; dropwise adding 320.0kg diethyl malonate (1eq) and 843.1kg 2 dibromoisopropyl ether (1:1.0eq) mixed solution, after dropping, keep warm at 63±2°C for 3h, after the reaction is complete, cool the system down to 20-30°C, add the reaction system to 320kg water (1g / 1mL) and 277.4kg ethylbenzene (1g / 1mL) extraction, liquid separation to obtain an organic phase;

[0033] (2) Hydrolysis: Add 768kg (1g / 2mL) of prepared 50% sodium hydroxide solution to the organic phase system obtained in step (1), heat up the system to 85±5°C, keep it warm at 85±5°C for 10h, and the reaction is complet...

Embodiment 3

[0035] Embodiment 3: A kind of one-pot method prepares 2,6-dinitro-4-formic acid pyran The method is characterized in that the specific preparation steps are as follows:

[0036] (1) Ring closure: Add 1290kg xylene (1g / 10mL) to a 5000L reactor, start stirring, then add 414.0kg anhydrous potassium carbonate (1:3.0eq) and 52.2kg tetrabutylammonium chloride (1 : 0.2eq), the temperature was raised to 48±2°C; 150.0kg diethyl malonate (1eq) and 781.9kg 1,1'-dinitro-2,2'-diiodoethyl ether were added dropwise (1:2.0eq) mixed solution, after dropping, keep warm at 48±2°C for 20h, after the reaction is complete, cool the system down to 20-30°C, add the reaction system to 1500kg water (1g / 10mL) and 1290kg xylene ( 1g / 10mL) extraction, liquid separation to obtain an organic phase;

[0037] (2) Hydrolysis: Add 1800kg (1g / 10mL) of prepared 50% potassium hydroxide solution to the organic phase system obtained in step (1), raise the temperature of the system to 70±5°C, keep it at 70±5°C f...

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Abstract

The invention relates to a preparation method of tetrahydropytanyl-4-formic acid and derivatives thereof by a one-pot process, which comprises the following steps: by using diethyl malonate which is industrialized in the market or easily prepared as an initial raw material, cyclizing with substituted dihalogenated ether (X is -Cl, -Br or -I), hydrolyzing, and decarboxylating to obtain the tetrahydropytanyl-4-formic acid and derivatives thereof. The method has the advantages of cheap and accessible raw materials, stable technological conditions and higher reaction purity and yield (the yield is 75.6-82.2%), is simple to operate in the whole production process, shortens the production time, enhances the yield, is suitable for large-scale production, and provides a new thinking and method for preparing the tetrahydropytanyl-4-formic acid and derivatives thereof.

Description

(1) Technical field: [0001] The invention relates to a method for preparing organic synthesis intermediates and pharmaceutical intermediates, in particular to a method for preparing tetrahydropyran-4-carboxylic acid and derivatives thereof in one pot. (two) background technology: [0002] Tetrahydropyran-4-carboxylic acid and its derivatives are important organic synthesis intermediates and pharmaceutical intermediates, and are also important intermediates for the synthesis of wittig reagents. It reacts with aldehydes or ketones to undergo Wittig reactions or carbonyl olefination reactions, Wittig Reagents and their reactions find numerous applications in the synthesis of the latest series of advanced and diverse classes of fine organic chemicals. Therefore, it is of great significance to develop a high-efficiency, low-cost synthesis process of tetrahydropyran-4-carboxylic acid and its derivatives. [0003] At present, the methods for preparing tetrahydropyran-4-carboxylic ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D309/08
Inventor 洪浩陈朝勇刘双勇
Owner ASYMCHEM LAB TIANJIN
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