Preparation method of chiral sertraline hydrochloride

A technology of sertraline hydrochloride and chirality is applied in the field of splitting of chiral sertraline hydrochloride to achieve the effects of less three wastes, high efficiency and convenient post-processing

Active Publication Date: 2015-06-17
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
  • Preparation method of chiral sertraline hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Add 306 g (1 mole) of racemic sertraline and 552 g (2 moles) of chiral D-1-methyl-3-propylimidazolium mandelate ionic liquid into a 2L three-neck flask, at 50°C After reacting for 5 hours, add 306 milliliters of absolute ethanol and stir for 1 hour, filter to obtain filter cake a and filtrate a, add 50 milliliters of 10% sodium hydroxide aqueous solution to filter cake a and stir at room temperature for 1 hour for hydrolysis, and then Add 3 × 100 ml of dichloromethane for extraction three times, combine the dichloromethane extracts and add 20% aqueous hydrochloric acid with mass concentration under stirring at room temperature until no new precipitates are formed, filter to obtain filter cake b and filtrate b, filter cake b is 137 grams of Cis-(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthylamine hydrochloride, The yield is 80%. Melting point: 248~250℃, optical purity ≥98.0%, content ≥99.0%.

Embodiment 2

[0024] Add 306 g (1 mole) of racemic sertraline and 828 g (3 moles) of chiral D-1-methyl-3-butylimidazole mandelate ionic liquid into a 2L three-neck flask, at 80°C After reacting for 3 hours, add 1530 milliliters of absolute ethanol and stir for 1 hour, filter to obtain filter cake a and filtrate a, add 50 milliliters of mass concentration 10% sodium hydroxide aqueous solution to filter cake a and stir at room temperature for 1 hour to carry out hydrolysis, then Add 3 × 100 ml of dichloromethane for extraction three times, combine the dichloromethane extracts and add 20% aqueous hydrochloric acid with mass concentration under stirring at room temperature until no new precipitates are formed, filter to obtain filter cake b and filtrate b, filter cake b is 139 grams of Cis-(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthylamine hydrochloride, Yield 81.2%. Melting point: 248~250℃, optical purity ≥98.0%, content ≥99.0%.

Embodiment 3

[0026]Add 306 grams (1 mole) of racemic sertraline and 664 grams (2 moles) of chiral D-1-methyl-3-hexylimidazole mandelate ionic liquid into a 2L three-necked flask, and react at 50°C After 5 hours, add 918 milliliters of absolute ethanol and stir for 1 hour, filter to obtain filter cake a and filtrate a, add 50 milliliters of 10% sodium hydroxide aqueous solution to filter cake a, stir at room temperature for 1 hour for hydrolysis, and then add Extract three times with 3×100 ml of dichloromethane, combine the dichloromethane extracts and add 20% hydrochloric acid aqueous solution under stirring at room temperature until no new precipitate is formed, filter 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 138 grams, received The rate is 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 resolution method of chiral sertraline hydrochloride, in particular to a resolution method of chiral sertraline hydrochloride by using 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 listed by Pfizer in the early 1990s. Sertraline hydrochloride is the latest in a class of selective 5-HT recycle inhibitors (SSRI), which can help improve the body's ability to effectively relieve patients' depressive symptoms, including restlessness, and can reduce persistent fatigue symptoms and state of anxiety. It has been widely used in the treatment of depressive and obsessive-compulsive disorders 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 Patents(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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