Preparation method of chiral sertraline hydrochloride

A technology of sertraline hydrochloride and chirality, which is applied in the field of splitting of chiral sertraline hydrochloride, and achieves the effects of high efficiency, less three wastes and easy operation

Active Publication Date: 2014-02-12
上海衡山药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the cost and recycling of resolution reagents applied in chemical resolution methods is a key issue at present

Method used

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  • Preparation method of chiral sertraline hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] 306 g (1 mol) of racemic sertraline and 552 g (2 mol) of chiral D-1-methyl-3-propylimidazole mandelate ionic liquid were added to a 2L three-necked flask, and the mixture was heated at 50°C. After 5 hours of reaction, 306 ml of absolute ethanol was added and stirred for 1 hour, and filtered to obtain filter cake a and filtrate a. 50 ml of 10% aqueous sodium hydroxide solution was added to filter cake a, and stirred for 1 hour at room temperature for hydrolysis, and then Add 3×100 ml of dichloromethane to extract three times, combine the dichloromethane extracts and add 20% hydrochloric acid aqueous solution at room temperature under stirring until no new precipitates are formed, filter to obtain filter cake b and filtrate b, filter cake b is Cis-(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthylamine hydrochloride 137g, Yield 80%. Melting point: 248~250℃, optical purity ≥98.0%, content ≥99.0%.

Embodiment 2

[0024] 306 g (1 mol) of racemic sertraline and 828 g (3 mol) of chiral D-1-methyl-3-butylimidazolium mandelate ionic liquid were added to a 2L three-necked flask, and the mixture was heated at 80°C. After 3 hours of reaction, 1530 ml of absolute ethanol was added and stirred for 1 hour, and filtered to obtain filter cake a and filtrate a. In filter cake a, 50 ml of 10% aqueous sodium hydroxide solution was added and stirred for 1 hour at room temperature for hydrolysis, and then Add 3×100 ml of dichloromethane to extract three times, combine the dichloromethane extracts and add 20% hydrochloric acid aqueous solution at room temperature under stirring until no new precipitates are formed, filter to obtain filter cake b and filtrate b, filter cake b is Cis-(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthylamine hydrochloride 139 g, Yield 81.2%. Melting point: 248~250℃, optical purity ≥98.0%, content ≥99.0%.

Embodiment 3

[0026]306 g (1 mol) of racemic sertraline and 664 g (2 mol) of chiral D-1-methyl-3-hexylimidazolium mandelate ionic liquid were added to a 2L three-necked flask and reacted at 50 °C After 5 hours, 918 ml of anhydrous ethanol was added and stirred for 1 hour, filtered to obtain filter cake a and filtrate a, 50 ml of 10% aqueous sodium hydroxide solution was added to filter cake a, stirred for 1 hour at room temperature for hydrolysis, and then added Dichloromethane was extracted three times with 3 × 100 ml, the dichloromethane extracts were combined and 20% aqueous hydrochloric acid solution was added under stirring at room temperature until no new precipitates were formed, and filtered to obtain filter cake b and filtrate b, filter cake b That is Cis-(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthylamine hydrochloride 138g, received rate 81%. Melting point: 248~250℃, optical purity ≥98.0%, content ≥99.0%.

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Abstract

The invention discloses a preparation method of chiral sertraline hydrochloride. The method comprises the following steps: mixing racemic sertraline and a chiral ionic liquid of D-mandelic acid; slowly stirring at 10-100 DEG C for full reaction; after reaction, adding absolute ethyl alcohol into the reaction mixed liquid for continuously stirring for 1 hour; filtering; hydrolyzing the filter cakes; acidizing by hydrochloric acid to obtain Cis-(1S, 4S)-sertraline hydrochloride; and recovering the filtrate to obtain the chiral ionic liquid which is recycled. According to the invention, the chiral ionic liquid is taken as a solvent and a resolving agent, so that the yield is greater than or equal to 80%, the optical purity is greater than or equal to 98.0%, and the content is greater than or equal to 99.0%. The method is simple and convenient to operate, high in efficiency, less in three wastes and convenient in post-treatment, and the ionic liquid can be repeatedly used, so that the preparation method is an economical and practical green and environment-friendly technology.

Description

(1) Technical field [0001] The invention relates to a method for separating chiral sertraline hydrochloride, in particular to a method for separating chiral sertraline hydrochloride by utilizing chiral D-mandelic acid ionic liquid. (2) Background technology [0002] Sertralin Hydrochloride, CAS accession number is [79559-97-O], chemical name is Cis-(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3 ,4-Tetrahydro-N-methyl-1-naphthylamine hydrochloride, is an antipsychotic depressant newly developed and marketed by Pfizer in the early 1990s. Sertraline hydrochloride is the latest in a class of selective 5-HT recycling inhibitors (SSRIs), which can help improve the body and effectively reduce patients' depressive symptoms, including irritability, and can reduce persistent symptoms of fatigue and Anxiety state. It has been widely used in the treatment of depression and obsessive-compulsive disorder in the world. Sertraline has the characteristics of long-acting, low toxicity to liver cells...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C211/42C07C209/88
Inventor 裴文孙莉胡卫雅陶荣哨
Owner 上海衡山药业有限公司
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