Unlock instant, AI-driven research and patent intelligence for your innovation.

Method for preparing (S)-citalopram intermediate S-type glycol

A technology of d-citalopram and type diol, which is applied in the direction of organic chemistry methods, chemical instruments and methods, and organic racemization, can solve problems such as poor stability and reproducibility, high cost, and difficulty, and achieve stability Good performance and reproducibility, low cost and easy operation

Active Publication Date: 2011-03-16
ZHEJIANG AOTUOKANG PHARMA GROUP
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0026] The present invention aims at the disadvantages of high cost, low yield, cumbersome operation, high difficulty, poor stability and reproducibility, and unsuitability for industrialized production in the existing method for preparing single optical isomer D-citalopram The purpose is to provide a method for resolution of the D-citalopram intermediate S-type diol with low cost, easy operation, good stability and reproducibility, and suitable for industrial production.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for preparing (S)-citalopram intermediate S-type glycol
  • Method for preparing (S)-citalopram intermediate S-type glycol
  • Method for preparing (S)-citalopram intermediate S-type glycol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] 55.1g 4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-cyanobenzene in 100ml dichloromethane solution and D - Mix 32.5 g of p-methyldibenzoyl tartaric acid in 500 ml of absolute ethanol and heat until the solids are completely dissolved. Slowly lowered to room temperature, then lowered to 0°C, stirred for 1h. Filter and wash with a small amount of dichloromethane: absolute ethanol (1:5). dry. 32.1 g of 4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-cyanobenzene.1 / 2 DTTA salt was obtained. rate of 36.7%.

[0040] The above solid was dissolved in 400 ml of a mixed solvent of dichloromethane and absolute ethanol (ratio 1:5) for recrystallization to obtain 29.1 g of solid, with a yield of 93%.

[0041] After detection: the total yield of resolution: 34.1%; the optical degree is 99.4% (HPLC).

Embodiment 2

[0043] 55.1g 4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-cyanobenzene in 150ml dichloromethane solution and D - Mix 32.5 g of p-methyldibenzoyl tartaric acid in 350 ml of absolute ethanol and heat until the solids are completely dissolved. Slowly lowered to room temperature, then lowered to 0°C, stirred for 1h. Filter and wash with a small amount of dichloromethane: absolute ethanol (3:5). dry. 34.5 g of 4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-cyanobenzene.1 / 2 DTTA salt was obtained. rate 39.4%.

[0044] The above solid was dissolved in 350 ml of a mixed solvent of dichloromethane and absolute ethanol (ratio 3:5) for recrystallization to obtain 32.8 g of solid, with a yield of 95%.

[0045] After detection: the total yield of resolution: 37.4%; the optical degree is 99.6% (HPLC).

Embodiment 3

[0047] 55.1g of 4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-cyanobenzene in 450ml of dichloromethane solution and D - Mix 32.5 g of p-methyldibenzoyl tartaric acid in 150 ml of absolute ethanol and heat until the solids are completely dissolved. Slowly lowered to room temperature, then lowered to 0°C, stirred for 1h. Filter and wash with a small amount of dichloromethane: absolute ethanol (3:1). dry. 40.5 g of 4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-cyanobenzene.1 / 2 DTTA salt was obtained. The rate is 46.3%.

[0048] The above solid was dissolved in 350 ml of a mixed solvent of dichloromethane and absolute ethanol (ratio 3:1) for recrystallization to obtain 39.0 g of solid, with a yield of 96%.

[0049]After testing: the total yield of resolution: 44.4%; the optical degree is 99.0% (HPLC).

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
optical purityaaaaaaaaaa
optical purityaaaaaaaaaa
Login to View More

Abstract

The invention relates to a method of preparing S-type diol that is a dextral citalopram intermediate product. Aiming at the disadvantages of high cost, low yield rate, fussy operation, high difficulty, and bad stability and repeatability in the existing method of preparing dextral citalopram that has single optical isomers, the invention provides a separation method of the S-type diol that is thedextral citalopram intermediate product which has low cost, convenient operation, and good stability and repeatability. The method is completed by the following way: racemic glycols (IV) are separated by adopting a separation method; resolving agent used for separation is organic acid that has the single optical isomers; resolving solvent used for separation is mixed solvent composed of halogenated hydrocarbon and absolute ethyl alcohol, or the mixed solvent composed of acetone and the absolute ethyl alcohol, or the acetone and isopropanol; when in separation, the racemic glycols (IV) are putin the mixed solution composed of the resolving agent and the resolving solvent, the salt of the S-type diol is crystallized and precipitated, and the S-type diol (I) which has single optical configurations is obtained through dissociation.

Description

technical field [0001] The invention relates to a preparation method of citalopram intermediate diol, in particular to a preparation method of D-citalopram intermediate S-type diol. Background technique [0002] Citalopram, a well-known antidepressant that has been on the market for many years, is a selective serotonin reuptake inhibitor, and the antidepressant activity of this compound has been reported in various publications, such as: prog. Neuro-Psychopharmacol. & Biol.Psychiat.1982 (6): 277-295, Acta Psychiatr. Scand., 1987 (75): 478-486. In EP 474580, it is further disclosed that the compound is effective in the treatment of dementia and cerebrovascular disease The effect shown in . At present, it has been listed in more than 60 countries and regions in the world. The commercially available citalopram is a racemate, and its structure is as follows: [0003] [0004] Formula (II) [0005] The patents for the first synthesis of citalopram are US Patent US4136193 in...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07C255/59C07C253/34C07B57/00
Inventor 朱雪焱叶晓秧吴新建袁哲东施华琴王强
Owner ZHEJIANG AOTUOKANG PHARMA GROUP