Application of bonded 3,5-dimethylcarbaniloylated beta-cyclodextrin chiral stationary phase in chiral analysis and/or separation of sertraline hydrochloride intermediate (+/-)-Tetralone

A technology of dimethylaniline carbamoyl and chiral stationary phase, which is applied in the field of analysis and separation of chiral compounds, can solve the problems of limitations, coating-type chiral stationary phases are prone to swelling or dissolution, and achieve stable quality , good separation effect, high separation effect

Inactive Publication Date: 2015-08-12
广州研创生物技术发展有限公司
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  • Description
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Problems solved by technology

In the Chinese invention patent application CN201410315738.7, the application of coated cellulose / amylose-tris(3,5-dimethylphenylcarbamate) chiral fixed phase for chromatographic analysis, the maximum resolution Rs is 2.037, however, the coating-type chiral stationary phase is prone to swelling or dissolving in unconventional mobile phases, and its application in preparative chromatography is subject to certain restrictions

Method used

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  • Application of bonded 3,5-dimethylcarbaniloylated beta-cyclodextrin chiral stationary phase in chiral analysis and/or separation of sertraline hydrochloride intermediate (+/-)-Tetralone
  • Application of bonded 3,5-dimethylcarbaniloylated beta-cyclodextrin chiral stationary phase in chiral analysis and/or separation of sertraline hydrochloride intermediate (+/-)-Tetralone
  • Application of bonded 3,5-dimethylcarbaniloylated beta-cyclodextrin chiral stationary phase in chiral analysis and/or separation of sertraline hydrochloride intermediate (+/-)-Tetralone

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Experimental program
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Embodiment approach

[0057] 1. Selection of mobile phase

[0058] The mobile phase composition affects the separation of (±)-Tetralone racemate and also affects the production efficiency of the simulated moving bed. As shown in Table 1, as the polarity of the mobile phase decreases (replacing ethanol with isopropanol, or reducing the alcohol content), the separation of (±)-Tetralone enantiomers on the chiral stationary phase increases, and the selectivity factor become larger, but the prolongation of the retention time will significantly reduce the production efficiency of the equipment and increase the solvent consumption, so follow-up work is carried out with n-hexane:alcohol=90:10 (v / v).

[0059] Table 1 Selection of mobile phase

[0060]

[0061] Test conditions: Shimadzu LC-15C liquid chromatograph; column specification: I.D.4.6×250mm; filler is bonded 3,5-dimethylphenylcarbamoylated β-cyclodextrin chiral stationary phase (5 μm) ; Detection wavelength: 214nm; Flow rate: 1.0mL min -1 . ...

example 1

[0070] a. Operating conditions

[0071] Mobile phase: n-hexane: ethanol = 90:10 (v / v)

[0072] Injection concentration: 0.50mg·mL -1

[0073] Injection liquid flow rate: 0.05mL min -1

[0074] Eluent flow rate: 1.80mL min -1

[0075] Raffinate flow rate: 1.25mL min -1

[0076] Extraction flow rate: 0.60mL min -1

[0077] Switching time: 5min

[0078] System temperature: 25°C

[0079] b. Product analysis

[0080] The simulated moving bed was operated continuously for 24 hours, the sample solution was collected at the raffinate outlet and the extraction outlet respectively, and then the product was analyzed. In the raffinate, the purity of (4S)-(+)-Tetralone was 95.64%; in the extract, the purity of (4R)-(-)-Tetralone was 95.44%. Each kilogram of chiral stationary phase can produce 0.50g of two isomer products each day, the consumption of mobile phase is 74L / g, and the recovery rate of the product is 94%.

example 2

[0082] a. Operating conditions

[0083] Mobile phase: n-hexane:isopropanol=90:10(v / v)

[0084] Injection concentration: 0.50mg·mL -1

[0085] Injection liquid flow rate: 0.10mL min -1

[0086] Eluent flow rate: 1.80mL min -1

[0087] Raffinate flow rate: 0.90mL min -1

[0088] Extraction flow rate: 1.00mL min -1

[0089] Switching time: 5min

[0090] System temperature: 25°C

[0091] b. Product analysis

[0092] The simulated moving bed was operated continuously for 24 hours, the sample solution was collected at the raffinate outlet and the extraction outlet respectively, and then the product was analyzed. In the raffinate, the purity of (4S)-(+)-Tetralone was 96.69%; in the extract, the purity of (4R)-(-)-Tetralone was 97.69%. Each kilogram of chiral stationary phase can produce 1.00g of two isomer products every day, the consumption of mobile phase is 37L / g, and the recovery rate of the product is 90.64%.

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Abstract

The invention discloses application of a bonded 3,5-dimethylcarbaniloylated beta-cyclodextrin chiral stationary phase in chiral analysis and/or separation of a sertraline hydrochloride intermediate (+/-)-Tetralone. The invention also discloses application of the bonded 3,5-dimethylcarbaniloylated beta-cyclodextrin chiral stationary phase in chiral separation of a sertraline hydrochloride intermediate (+/-)-Tetralone by simulated moving bed chromatography. The cyclodextrin chiral stationary phase can have better separating effects than the existing chiral stationary phases under identical conditions. The separation method, which adopts a four-region simulated moving bed system and uses a bonded 3,5-dimethylcarbaniloylated beta-cyclodextrin chiral stationary phase as a chiral column filler and an n-hexane-fatty alcohol mixed solution as a mobile phase, has the advantages of continuous sampling, high automation degree, high product purity and low mobile phase consumption, is suitable for industrialized chromatographic separation on (+/-)-Tetralone to obtain the optically Tetralone isomer product, and widens the application range of the cyclodextrin chiral stationary phase in the preparative chromatography system.

Description

technical field [0001] The invention relates to the field of analysis and separation of chiral compounds, in particular to the chiral stationary phase bonded with 3,5-dimethylphenylcarbamoylated β-cyclodextrin in the middle of chiral analysis and / or separation of sertraline hydrochloride Application of body (±)-Tetralone. Background technique [0002] Chirality is ubiquitous in nature. Enantiomers with different spatial conformations may exhibit completely different pharmacological activities, metabolic processes or toxicity in vivo. Rapid and efficient acquisition of optically pure chiral drugs and their intermediates has become one of the current research hotspots. Among them, chromatographic separation technology can not only perform qualitative and quantitative analysis of chiral enantiomers, but also be used for preparative-scale separation. [0003] Sertraline hydrochloride is an antipsychotic drug developed by Pfizer Pharmaceutical Co., Ltd. of the United States in...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): B01J20/29B01D15/22C08B37/16C07C49/333C07C45/79G01N30/02
Inventor 章伟光陈贤铬范军徐俊烨
Owner 广州研创生物技术发展有限公司
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