A kind of preparation method of levocloperastine fendizaic acid

The technology of leverastin and cloperastine, which is applied in the field of chemical drug synthesis, can solve the problems of low total yield in the preparation process, and achieve the effects of reducing three-waste pollution, reducing costs and high safety.

Active Publication Date: 2017-06-16
CHONGQING HENG AN CHEM CO LTD
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

The levocloperastine fendizaic acid obtained by the method has the advantage of higher optical purity, but the total yield of the preparation process is low

Method used

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  • A kind of preparation method of levocloperastine fendizaic acid
  • A kind of preparation method of levocloperastine fendizaic acid
  • A kind of preparation method of levocloperastine fendizaic acid

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preparation example Construction

[0037] The invention provides a kind of preparation method of L-cloperastine fendizac acid, comprising the following steps:

[0038] Use a resolving agent to resolve racemic cloperastine in an aliphatic alcohol solvent to obtain levocloperastine. The resolving agent is L-(-)-diR substituted benzoyl tartaric acid, and the R is alkyl, alkoxy, -Cl, -F, -Br or -H;

[0039] The levo-cloperastine is subjected to a salt-forming reaction with fendisic acid to obtain levo-cloperastine fendisic acid.

[0040] The method provided by the invention uses L-(-)-diR substituted benzoyl tartaric acid as a resolving agent to resolve racemic cloperastine in an aliphatic alcohol solvent, and the resolution yield is high, so that the obtained The levocloperastine fendioleic acid has high optical purity and high product yield.

[0041] In addition, the resolving agent and fatty alcohol solvents used in the resolution of racemic cloperastine in the present invention can be used repeatedly, which r...

Embodiment 1

[0113] Into a dry and clean 1000mL three-necked reaction flask, add 300g (1.373mol) 4-chlorobenzhydryl alcohol, 150g (1.863mol) 2-chloroethanol and 350mL toluene in sequence, and stir to dissolve;

[0114] Slowly add 50 g of concentrated sulfuric acid dropwise to the dissolved solution, heat to reflux at a heating rate of 4°C / min, and react for 5 hours;

[0115] Cool the obtained reaction product to room temperature, add 100mL of water to it for extraction, neutralize it with 42% liquid caustic soda until the pH value of the water layer reaches 7, and separate the water layer;

[0116] The organic layer was distilled under reduced pressure to recover toluene, distilled to an internal temperature of 120°C, and a vacuum of -0.08 MPa or higher to obtain 390 g of an oily substance.

[0117] Put the above 390g oil into a 2000mL dry and clean three-necked reaction flask, add 150g of anhydrous sodium carbonate and 180g (2.118mol) of piperidine to it, and heat it to 95°C at a heating ...

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Abstract

The invention discloses a preparation method of levo cloperastine fendizoate, which comprises the following steps: carrying out nucleophilic substitution reaction on 4-chlorobenzhydrol and 2-chloroethanol in a benzene organic solvent, so that an intermediate product is obtained; reacting the intermediate product with piperidine, so that racemic cloperastine is obtained; resolving the racemic cloperastine by using a resolving agent in a fatty alcohol solvent, so that levo cloperastine is obtained; and carrying out salt forming reaction on the levo cloperastine and a fendizoic acid, so that levo cloperastine fendizoate is obtained, wherein the resolving agent is an R-substituted dibenzoyl-L-tartaric acid, and R refers to alkyl, alkoxy, -Cl, -F, -Br or -H. In the method provided by the invention, in a fatty alcohol solvent, an R-substituted dibenzoyl-L-tartaric acid is adopted as a resolving agent for carrying out resolving on racemic cloperastine, and the resolving yield is high, so that the obtained levo cloperastine fendizoate has high optical purity, and has a high product yield.

Description

technical field [0001] The invention relates to the technical field of chemical drug synthesis, in particular to a preparation method of L-cloperastine fendizaic acid. Background technique [0002] Racemic cloperastine itself has good biological activity and drug activity. It is a central antitussive drug, which mainly inhibits the cough center and antitussive. It also has a weak antihistamine effect and has no addiction and tolerance. It is clinically used for cough caused by upper respiratory tract infection. However, levocloperastine fendecic acid has higher clinical drug activity, and its curative effect is many times that of racemic cloperastine. It basically has no side effects, and it can be used as a medicine for children, so the market demand for this product is large. , the outlook is good. [0003] At present, the known preparation methods of L-cloperastine fendizaic acid mainly include: if racemic 4-chlorobenzhydryl alcohol is used as a starting material, it is...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D295/088
CPCC07D295/088
Inventor 陶文潘潘文驰潘兴长罗泳萍樊希祥
Owner CHONGQING HENG AN CHEM CO LTD
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