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Preparation method of clomezanone intermediate

A technology of clomezadone and intermediates, applied in the field of pharmaceuticals, can solve the problems of unfavorable production and operator health, high reaction temperature, long reaction time, etc., reduce side reactions and impurity generation, easy control of conditions, and simple operation Effect

Active Publication Date: 2022-02-15
广州隽沐生物科技股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the use of benzene or toluene as the reaction environment is highly toxic, unfavorable for the health of production operators, and the temperature of the reaction is high, and the reaction time is long, which is limited in the actual process of preparation, and the conversion rate is low, and side reactions More, so that the purity of the product is lower

Method used

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  • Preparation method of clomezanone intermediate
  • Preparation method of clomezanone intermediate
  • Preparation method of clomezanone intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] A kind of preparation method of clomezalone intermediate, comprises the steps:

[0049] (1) Preparation of precursor: add 7.03g 4-chlorobenzaldehyde in the reaction flask, add 16.88g methylamine hydrochloride (5eq) and 21.00g sodium bicarbonate (5eq), mix, and Stir evenly with a mechanical stirrer, until more liquid occurs in the system, get the liquid in the system and carry out gas phase detection, when detecting that the 4-chlorobenzaldehyde raw material content is lower than 5% of the original addition, then the 4-chlorobenzaldehyde is basically The response is complete. Then add cyclohexane to the system for extraction, the amount of cyclohexane for each extraction is 50mL, and the extraction is repeated 4 times. After the extraction was completed, the organic phase obtained was dried with anhydrous sodium sulfate, and then treated by rotary evaporation to obtain 6.45 g of the precursor.

[0050] (2) Preparation of clomezalone intermediate: take 4.61g of the prec...

Embodiment 2

[0079] A kind of preparation method of clomezalone intermediate, comprises the steps:

[0080] (1) Prepare the precursor: add 7.03g 4-chlorobenzaldehyde to the reaction flask and dissolve in 21mL cyclohexane, add 10.13g methylamine hydrochloride (the equivalent is 3eq) and 20.73g potassium carbonate (the equivalent is 5eq), Mix, and stir evenly with mechanical stirrer under room temperature, until there is more liquid to occur in the system, get the liquid in the system and carry out gas-phase detection, when detecting that 4-chlorobenzaldehyde raw material content is lower than 5% of original addition, then 4 - Chlorobenzaldehyde basically reacts completely. Then add cyclohexane to the system for extraction, the amount of cyclohexane for each extraction is 50mL, and the extraction is repeated 4 times. The organic phase obtained after the extraction was dried with anhydrous sodium sulfate, and then processed by rotary evaporation to obtain 6.30 g of the precursor, and the pur...

Embodiment 3

[0083] A kind of preparation method of clomezalone intermediate, comprises the steps:

[0084] (1) Prepare the precursor: add 7.03g 4-chlorobenzaldehyde to the reaction flask and dissolve in 21mL n-heptane, add 13.50g methylamine hydrochloride (4eq equivalent) and 42.45g potassium phosphate (5eq equivalent), Mix, and stir evenly with a mechanical stirrer at room temperature, until there are more liquids in the system, get the liquid in the system and carry out gas phase detection, when it is detected that the 4-chlorobenzaldehyde content is lower than 5% of the original addition, then 4- The reaction of chlorobenzaldehyde is basically complete. Then add cyclohexane to the system for extraction, the amount of cyclohexane for each extraction is 50mL, and the extraction is repeated 4 times. After the extraction was completed, the organic phase obtained was dried with anhydrous sodium sulfate, and then processed by rotary evaporation to obtain 6.40 g of the precursor, and the pur...

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Abstract

The invention relates to the field of pharmacy, in particular to a preparation method for a clomezanone intermediate. The preparation method comprises the following steps: (1) precursor preparation: subjecting 4-chlorobenzaldehyde, methylamine hydrochloride and an alkaline regulator to mixing and stirring, adding an extraction solvent A for extraction after the raw materials react completely, and subjecting an organic phase obtained after extraction to rotary evaporation to obtain a precursor; and (2) preparation of the clomezanone intermediate: mixing the prepared precursor with a reaction solvent A, then adding 3-mercaptopropionic acid, carrying out heating and refluxing to separate water, carrying out cooling after the raw materials are completely reacted, performing rotary evaporation, adding a washing solution into rotary evaporation residues, carrying out uniform mixing, then adding an extraction solvent B, carrying out extracting, separating liquid, washing an organic phase obtained after liquid separation with water, and performing rotary drying so as to prepare the clomezanone intermediate. The preparation method is easy and convenient to operate, conditions are easy to control, industrial production and preparation are facilitated, materials with large toxicity such as benzene or methylbenzene are not added, and the influence of solvents with large toxicity on the environment and operators is reduced.

Description

technical field [0001] The application relates to the field of pharmacy, more specifically, it relates to a preparation method of clomezalone intermediate. Background technique [0002] Clomezalone is an over-the-counter drug for sedation and sleep aids. It has the effects of anti-anxiety, sedation, hypnosis and muscle tension relief. , restlessness, insomnia, alcoholism, muscle pain and spastic rheumatoid arthritis, etc. [0003] The chemical name of clomezalone is 2-p-chlorophenyl-3-methyl-1,3-hydrobuprofezin-[4]-1,1-dioxide, and the molecular formula is C 11 h 12 C l NO 3 S, the molecular weight is 273.74. In the process of synthesizing clomezalone, the chemical name is 2-(4-chlorophenyl)-3-methyl-1,3-tetrahydrothiazin-4-one, and the molecular formula is C 11 h 12 C l NOS and clomezalone intermediate with a molecular weight of 241.7330 are the key reaction precursors for the synthesis of clomezalone. The current synthesis method of the clomezalone intermediate is...

Claims

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Application Information

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IPC IPC(8): C07D279/06C07C249/02C07C251/24
CPCC07D279/06C07C249/02C07C251/24Y02P20/55
Inventor 赖金强丁家豪邹小燕
Owner 广州隽沐生物科技股份有限公司