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Preparation method of 2, 4-dimethyl oxazole-5-formic acid

A technology of dimethyloxazole and dimethyloxazole, applied in the direction of organic chemistry, etc., can solve the problems of inability to meet the needs of industrial production, unknown synthesis route, etc.

Pending Publication Date: 2022-05-13
BAYECAO HEALTH IND RES INST (XIAMEN) CO LTD +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] 2,4-Dimethyloxazole-5-carboxylic acid (C 6 h 7 NO 3 ) is an important intermediate for the synthesis of anti-leishmaniasis drugs with the structure shown in formula I, but at present, 2,4-dimethyloxazole-5-carboxylic acid needs to be synthesized by a specific organic synthesis company, and the synthetic route is unknown. Unable to meet the needs of industrial production

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  • Preparation method of 2, 4-dimethyl oxazole-5-formic acid
  • Preparation method of 2, 4-dimethyl oxazole-5-formic acid

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[0030] In the present invention, the preparation method of 2,4-dimethyloxazole-5-carboxylic acid, comprising the following steps:

[0031] Ethyl 2-chloroacetoacetate and acetamide were mixed and condensed to give ethyl 2,4-dimethyloxazole-5-carboxylate;

[0032] The ethyl 2,4-dimethyloxazole-5-carboxylate, inorganic strong base, polar organic solvent and water was mixed to hydrolyze to give 2,4-dimethyloxazole-5-carboxylic acid.

[0033] The present invention is ethyl 2-chloroacetoacetate and acetamide mixed, for condensation reaction, to give 2,4-dimethyloxazole-5-carboxylate ethyl ester. In the present invention, the molar ratio of ethyl 2-chloroacetoacetate to acetamide is preferably 1: 2 to 5, more preferably 1: 2.5 to 4.5. The present invention has no special requirements for the mixing sequence; the condensation reaction is preferably carried out under stirred conditions, the present invention has no special requirements for the specific embodiment of the stirring process.

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Embodiment 1

[0056] In the reactor, 44g of ethyl 2-chloroacetoacetate was added, 34g of acetamide was added, stirred at 120 °C for 24h. TLC monitoring the reaction process, at the end of the reaction added 50mL of water quenching reaction, and then added 100mL of ethyl acetate for extraction, and then the extraction phase at 35 °C rotary distillation to remove ethyl acetate, to obtain a crude product, with 20mL petroleum ether recrystallization, filtered to 2,4-dimethyloxazole-5-carboxylate ethyl ester. The yield was 83.6% and the purity was 98.7%.

[0057] 12g of 2,4-dimethyloxazole-5-carboxylate ethyl ester was dissolved in 100mL tetrahydrofuran, 8.5g lithium hydroxide was dissolved in 250mL of water, and then the two were mixed, and the reaction was 2h at 25 °C. TLC monitors the reaction progress, the reaction ends, first spin steaming at 35 °C to remove tetrahydrofuran, and then adjust the pH of the solution with 15% hydrochloric acid to 2, precipitate the solid, filter. The solid was diss...

Embodiment 2

[0059]4.4g 2-chloroacetoacetate was added to the reactor, 3.4g of acetamide was added, stirred at 110 °C for 20h. TLC monitoring the reaction process, the end of the reaction added 10mL of water quenching reaction, and then added 20mL of ethyl acetate for extraction, and then the extraction phase at 36 °C rotary steaming to remove ethyl acetate, to obtain a crude product, with 5mL petroleum ether recrystallization, filtered to give 2,4-dimethyloxazole-5-carboxylate ethyl ester. The yield was 83.4% and the purity was 98.5%.

[0060] 1.5g of 2,4-dimethyloxazole-5-carboxylate ethyl ester was dissolved in 11mL of methanol, 0.9g of sodium hydroxide was dissolved in 25mL of water, and then the two were mixed, and the reaction was 3h at 20 °C. TLC monitors the reaction progress, the reaction ends, first spin steaming at 36 °C to remove methanol, and then adjust the solution with 10% hydrochloric acid to a pH of 2.5, precipitate the solid, filter. The solid was dissolved in 20mL n-heptan...

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Abstract

The invention provides a preparation method of 2, 4-dimethyl oxazole-5-formic acid, and belongs to the technical field of synthesis of medical intermediates. The preparation method comprises the following steps: mixing ethyl 2-chloroacetoacetate and acetamide, and carrying out condensation reaction to obtain ethyl 2, 4-dimethyl oxazole-5-carboxylate; and mixing the 2, 4-dimethyl oxazole-5-carboxylic acid ethyl ester, an inorganic strong base, a polar organic solvent and water, and carrying out a hydrolysis reaction to obtain the 2, 4-dimethyl oxazole-5-formic acid. According to the invention, ethyl 2-chloroacetoacetate and acetamide are used as raw materials, 2, 4-dimethyl oxazole-5-formic acid is obtained through condensation reaction and hydrolysis reaction, the operation is simple, the raw materials are easy to obtain, and the product is easy to purify; the 2, 4-dimethyl oxazole-5-formic acid prepared by the method is high in yield and purity, has good economic benefits, and is suitable for industrial production.

Description

Technical field [0001] The present invention relates to the field of pharmaceutical intermediate synthesis technology, particularly to a method for preparing a 2,4-dimethyloxazole-5-carboxylic acid. Background [0002] Leishmaniasis is a disease caused by parasitic protozoa belonging to the genus Leishmania, which is transmitted by the bite of an infected female diptera, which sucks blood to lay eggs. Leishmaniasis is a global public health problem, with nearly 500,000 people infected each year, of whom more than 5,000 die. There are three main forms of leishmaniasis: visceral leishmaniasis (also known as kala-azar, the most severe form of leishmaniasis), cutaneous leishmaniasis (the most common), and mucocutaneous leishmaniasis. Of these, visceral leishmaniasis is the most severe form, caused by the parasite Duxer's leishmania, which can be fatal if left untreated. [0003] The two main treatments for visceral leishmaniasis are the antimony derivatives antimony sodium gluconate...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D263/34
CPCC07D263/34
Inventor 汤须崇赵应伟林青
Owner BAYECAO HEALTH IND RES INST (XIAMEN) CO LTD