Preparation method of meclofenoxate hydrochloride

A technology of meclofenoxate hydrochloride and hydrochloride, which is applied in the field of preparation of meclofenoxate hydrochloride, can solve problems such as insufficient hydrochloride formation, high reaction temperature, and low product purity, and achieve stable quality and high yield The effect of high and high purity of the crude product

Active Publication Date: 2019-03-01
GUANGDONG HUANAN PHARMACEUTICAL GROUP CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The first method above requires the use of benzene as a solvent, high toxicity, high reaction temperature, and the crude hydrochloric acid is yellowish
The second method uses toluene as a solvent, the reaction temperature is high, the product purity is low, and there is a problem of insufficient hydrochloride formation, which is not suitable for industrialization

Method used

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  • Preparation method of meclofenoxate hydrochloride
  • Preparation method of meclofenoxate hydrochloride
  • Preparation method of meclofenoxate hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Put 50 g (0.26 mol) of p-chlorophenoxyacetic acid into dichloromethane in a single-necked bottle, and then add 47.5 g (0.40 mol) of thionyl chloride dropwise. After the dropwise addition, stir and react at 30°C. Concentration of the solvent gave an oil. Dichloromethane was added to the obtained oily substance, and at the same time, 26 g (0.28 mol) of dimethylaminoethanol (0.28 mol) of dichloromethane solution was added dropwise into the reaction flask, and the dropwise addition was completed in 30 minutes, and the reaction was stirred at room temperature. Add water to extract, the obtained organic layer, and the oily substance obtained by concentrating the solvent are added to 250ml of ethyl acetate, and hydrogen chloride gas is used to form hydrochloride until a large amount of solids are precipitated. After being kept at 25°C, it is filtered to obtain 66g of white solid, with a yield of 84.6 %, purity 99.8% (attached figure 1 ):

[0039] The reaction equation is as ...

Embodiment 2

[0042] Put 50 g (0.26 mol) of p-chlorophenoxyacetic acid into dichloromethane in a single-necked bottle, and then add 47.5 g (0.40 mol) of thionyl chloride dropwise. After the dropwise addition, reflux and stir the reaction. The reaction solution was spin-dried to obtain an oil. Dichloromethane was added to the obtained oily substance, and at the same time, 26 g (0.28 mol) of dimethylaminoethanol (0.28 mol) of dichloromethane solution was added dropwise into the reaction flask, and the dropwise addition was completed in 30 minutes, and the reaction was stirred at room temperature. Water was added for extraction, and the obtained organic layer was spin-dried. The obtained oil was added to 250ml of ethyl acetate, and hydrogen chloride gas was used to form hydrochloride, until a large amount of solids were precipitated, and filtered at 25 ° C to obtain 68 g of white solids, with a yield of 87.1% and a purity of 99.9% (attached figure 2 ):

Embodiment 3～ Embodiment 10

[0044] Except that the process parameters of embodiment 3~embodiment 10 are listed in table 1, all the other steps and methods are the same as embodiment 1.

[0045] Table 1 shows the process parameters, product purity and yield of Examples 3 to 12.

[0046]

[0047] As can be seen from Table 1, the process parameters adopted in Examples 3, 4, 5, and 6 fall within the scope of the present invention, that is, the mol ratio of p-chlorophenoxyacetic acid, thionyl chloride, and dimethylethanolamine is 1 : 1.5~3.0: 1.1~1.5 These examples have all obtained good yields, and the purity is also above 99.5%.

[0048] However, Examples 7, 8, 9, and 10 did not adopt the process parameters of the present invention, and their yields and purity were obviously not as good as those of Examples 3, 4, 5, and 6.

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Abstract

The invention discloses a preparation method of meclofenoxate hydrochloride. The preparation method comprises the following steps: (A), performing an acylating chlorination reaction on p-chlorophenoxyacetic acid and sulfoxide chloride to obtain p-chlorophenoxyacetyl chloride; (B), performing a condensation reaction on the p-chlorophenoxyacetyl chloride obtained in the step (A) and dimethylaminoethanol to obtain meclofenoxate free alkali; (C), producing the free alkali obtained in the step (B) into hydrochloride, preserving heat and filtering to obtain the meclofenoxate hydrochloride. By the preparation method, raw materials are easy to obtain, the reaction temperature is low, the operation is convenient, and a crude product is high in purity and stable in quality; the invention provides asynthesis route of the meclofenoxate hydrochloride, which is easier to operate, more environmentally friendly and more economical.

Description

technical field [0001] The invention relates to the field of organic medicinal chemistry, in particular to a preparation method of meclofenoxate hydrochloride. Background technique [0002] Meclofenoxate hydrochloride, also known as clofenoxate, is a central stimulant. The chemical name structural formula is: [0003] [0004] Meclofenoxate hydrochloride mainly acts on the cerebral cortex. It can promote the redox of brain cells, regulate the metabolism of nerve cells, increase the utilization of carbohydrates and have an excitatory effect on the inhibited central nervous system. Traumatic coma, enuresis in children, disturbance of consciousness, senile mental illness, various dementias, alcoholism, etc. [0005] At present, there are mainly two kinds of production processes at home and abroad: Japanese patent JP7901692 uses p-chlorophenoxyacetic acid and acid anhydride to react to obtain p-chlorophenoxyacetic anhydride, and then uses benzene as a solvent to perform est...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C213/08C07C219/06
CPCC07C51/60C07C213/06C07C213/08C07C219/06C07C59/68
Inventor 谭珍友黎万尚伟
Owner GUANGDONG HUANAN PHARMACEUTICAL GROUP CO LTD
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