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Method for preparing citalopram and S-citalopram

A C4-C7, organic solvent technology, applied in the direction of organic chemistry, can solve the problems of low solvent recovery rate, high production cost, large environmental pollution, etc., and achieve the effects of high solubility, increased production capacity, and simple post-processing

Active Publication Date: 2015-01-07
ZHEJIANG HUAHAI PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This kind of solvent has high solubility to raw materials and products, but it has high toxicity and low boiling point, which leads to low solvent recovery rate, high production cost and great environmental pollution.

Method used

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  • Method for preparing citalopram and S-citalopram
  • Method for preparing citalopram and S-citalopram
  • Method for preparing citalopram and S-citalopram

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Add 34.2 mol of diol compound (II) and 100 ml of methyl isobutyl ketone into a four-neck flask, stir to dissolve at room temperature, add 12 g of NaOH, add 50 ml of water, cool to 3°C, and then slowly dropwise add 100 ml of methyl alcohol A solution in which 27 g of p-toluenesulfonyl chloride was dissolved in isobutyl ketone was heated up to room temperature after the reaction was completed at 3°C. The layers were allowed to stand, and the aqueous layer was extracted once with 70ml of methyl isobutyl ketone; the combined organic layers were washed twice with 100ml of water each time. The yield of citalopram obtained by concentrating the organic layer was 83%, and the HPLC analysis result showed that the product had a purity of 99.6%.

Embodiment 2

[0027] Add 34.2mol S-diol compound (II') to the four-necked flask, add 100ml methyl isobutyl ketone, stir at room temperature to dissolve, add 12g NaOH, add 50ml water, cool to 3°C, and slowly add A solution of 27 g of p-toluenesulfonyl chloride was dissolved in 100 ml of methyl isobutyl ketone, and after the reaction was completed at 3° C., the temperature was raised to room temperature. The layers were allowed to stand, and the aqueous layer was extracted once with 70ml of methyl isobutyl ketone; the combined organic layers were washed twice with 100ml of water each time. The S-citalopram (I') obtained by concentrating the organic layer had a yield of 85%, and the HPLC analysis results showed that the product had a purity of 99.8%.

Embodiment 3

[0029] Add 34.2mol of diol compound (II) and 100ml of methyl isobutyl ketone into a four-necked flask, stir to dissolve at room temperature, add 12g of NaOH, add 50ml of water, cool to 3°C, and slowly add 100ml of A solution in which 16 g of methanesulfonyl chloride was dissolved in methyl isobutyl ketone was heated up to room temperature after the reaction was completed at 3°C. The layers were allowed to stand, and the aqueous layer was extracted once with 70ml of methyl isobutyl ketone; the combined organic layers were washed twice with 100ml of water each time. The yield of citalopram obtained by concentrating the organic layer was 80%, and HPLC analysis showed that the product had a purity of 99.5%.

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Abstract

The invention relates to a method of preparing citalopram and S-citalopram by carrying out cyclization reaction on a diol compound (II) or S-diol compound (II') in a nixed solvent of a C4-C7 ketone solvent and water and aryl sulfonyl chloride or alkyl sulfonyl chloride under an alkaline condition. The solvent used by the invention is great in solubility to reactants and products, so that the use level of the solvent is reduced, the yield is improved and meanwhile the method is good in post-treatment extraction effect and simple and convenient to operate. The compounds (II and II') are as shown in the specification.

Description

technical field [0001] The invention relates to a method for industrially preparing citalopram and S-citalopram. Background technique [0002] Citalopram, whose chemical name is 1-[3-(dimethylamino)propyl]-1-(4'-fluorophenyl)-1,3-dihydro-5-cyanoisobenzofuran, is a A new drug for the treatment of depression, it belongs to the selective serotonin reextraction inhibitors. Specifically as shown in structural formula I. Its S-configuration is the main active ingredient, also known as S-citalopram, and its specific structural formula is as shown in formula I'. [0003] [0004] The synthetic method of bibliographical report, generally use diol compound (II) and S-diol compound (II') as starting material, under alkaline condition, react with substituted sulfonyl chloride compound, in organic solvent and water mixed solution Among them, the target product citalopram (I) or S-citalopram (I') is obtained through esterification and cyclization. The organic solvents used in the r...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/87
CPCC07D307/87
Inventor 梁尊俊肖伟烽黄文锋胡斯琪彭才华
Owner ZHEJIANG HUAHAI PHARMA CO LTD
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