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Method for synthesizing montrlukast sodium intermediate by means of series catalysis of graphene palladium cobalt

A technology of ene palladium cobalt catalysis and montelukast sodium, applied in the direction of organic chemistry, can solve the problems of high rhodium and chiral ligands, the difficulty of synthesis of catalyst chiral ligands, etc., and achieve the effect of good selectivity

Inactive Publication Date: 2017-07-07
UNIV OF JINAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this catalyst requires high rhodium and chiral ligands. The synthesis cost of the catalyst and the synthesis difficulty of the chiral ligands are relatively large, and the ee value of the product alcohol can only reach 92%.

Method used

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  • Method for synthesizing montrlukast sodium intermediate by means of series catalysis of graphene palladium cobalt
  • Method for synthesizing montrlukast sodium intermediate by means of series catalysis of graphene palladium cobalt
  • Method for synthesizing montrlukast sodium intermediate by means of series catalysis of graphene palladium cobalt

Examples

Experimental program
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Effect test

example 1

[0020] Example 1, methyl [S-(E)]-2-[3-[3-[2-(7-chloro-2-quinolyl)vinyl]phenyl]-3-hydroxypropyl]benzoate Synthesis:

[0021] The first step: Take a dry 100mL three-neck round bottom flask and add 300mg (E)-1-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)prop-2-en-1- ol, 200mg methyl o-bromobenzoate, 20mg graphene-supported palladium-cobalt nanocapsules containing 10% palladium by mass fraction, add 20 milliliters of anhydrous N, N-dimethylformamide under nitrogen protection, then add dropwise 1.7mL dimethicone Isopropylamine, 95 o C for 10 hours, monitor the raw material (E)-1-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)prop-2-en-1-ol after complete reaction, stop the reaction, react The liquid is naturally cooled to room temperature; the anhydrous and oxygen-free environment of the reaction system should be controlled.

[0022] The second step: maintain the N of the reaction system 2 Protection, cooling in an ice-water bath, control the temperature of the reaction solution at 2-...

specific Embodiment 2

[0023]Specific embodiment 2: [S-(E)]-2-[3-[3-[2-(7-chloro-2-quinolyl) vinyl] phenyl]-3-hydroxypropyl] benzoic acid Synthesis of methyl esters: Step 1: Take a dry 100 mL three-necked round bottom flask and add 680 mg (E)-1-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)prop- 2-en-1-ol, 560mg methyl o-bromobenzoate, 50mg graphene-supported palladium-cobalt nanocapsules containing 10% palladium by mass fraction, added 30 mL of anhydrous isopropanol under nitrogen protection, and then added dropwise 3.9 mL of di Isopropylamine, 110 o C for 12 hours, monitor the raw material (E)-1-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)prop-2-en-1-ol After complete reaction, stop the reaction, react The liquid is naturally cooled to room temperature; the anhydrous and oxygen-free environment of the reaction system must be controlled.

[0024] The second step: maintain the N of the reaction system 2 Protection, under ice-water bath cooling, control the temperature of the reaction solution at 2~5 o...

specific Embodiment 3

[0025] Specific Example 3: [S-(E)]-2-[3-[3-[2-(7-chloro-2-quinolyl)vinyl]phenyl]-3-hydroxypropyl]benzoic acid The synthesis of methyl esters: the first step: take a dry 100 mL three-neck round bottom flask and add 682 mg (E)-1-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)prop -2-en-1-ol, 565 mg of methyl o-bromobenzoate, 54 mg of graphene-supported palladium-cobalt nanocatalyst recovered by filtration and recovery by washing with water and ethanol, and adding 30 mL of anhydrous isopropanol under nitrogen protection, Then dropwise add 3.9mL diisopropylamine, 110 o C for 12 hours, monitor the raw material (E)-1-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)prop-2-en-1-ol After complete reaction, stop the reaction, react The liquid is naturally cooled to room temperature; the anhydrous and oxygen-free environment of the reaction system must be controlled.

[0026] The second step: maintain the N of the reaction system 2 Protection, under ice-water bath cooling, control the temperatur...

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Abstract

The invention relates to a technology for chemical synthesis of a medicine intermediate, in particular to a method for synthesizing a montrlukast sodium intermediate-[S-(E)]-2-[3-[3-[2-(7-chlorine-2-quinolyl)vinyl]phenyl]-3-hydroxy propyl]methyl benzoate by means of series catalysis of graphene palladium cobalt. The method adopts two steps of coupling and reducing and a one-pot series catalytic system; the obtained intermediate product does not need to be separated; the method is simple in operation, high in yield and good in chiral selectivity, thus being suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of medicinal chemical synthesis, and in particular relates to a synthetic route method of a Montelukast sodium intermediate. Background technique [0002] The chemical name of Montelukast Sodium is: 2-(1-((1(R)-(3-(2-(7-chloro-2-quinolinyl)-(E)-vinyl) )phenyl)-3-(2-(2-hydroxy-2propyl)phenyl)-propylthio)methyl)cyclopropyl)sodium acetate, used as anti-asthma agent, anti-allergic agent, etc. First synthesized and developed by Canadian Merk-Frosst company, the company disclosed the structure and preparation method of the compound in Chinese patent CN1061407A, wherein 1-(S)-(3-(2-(7-chloroquinoline-2- Base)-(E)-vinyl)phenyl)-3-(2-(2-hydroxy-2-propyl)phenyl)propanol is selectively protected, and then 2-(1-(mercaptomethyl) base) cyclopropyl) methyl acetate for nucleophilic substitution of mercapto, further hydrolysis, salt formation to obtain montelukast sodium. Its synthetic route is shown in the following formula. [0...

Claims

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Application Information

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IPC IPC(8): C07D215/18
CPCC07D215/18
Inventor 高令峰郑庚修韩歆雨付凯王秋芬
Owner UNIV OF JINAN