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

Method for preparing montelukast sodium intermediate

A technology of montelukast sodium and intermediates, which is applied in the field of preparation of montelukast sodium intermediates, can solve the problems of many side reactions, harsh reaction conditions, complicated intermediate processes, etc., and achieve single product, simple purification, high reaction The effect of mild conditions

Inactive Publication Date: 2013-10-16
KAIHUI SCI & TECH DEV SHANGHAI
View PDF2 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The technical problem to be solved by the present invention is: in order to overcome the defects that the intermediate process of preparing montelukast sodium is complicated, the reaction conditions are harsh, the side reactions are many, and the purification process is complicated, and a preparation method for the intermediate of montelukast sodium is provided

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 montelukast sodium intermediate
  • Method for preparing montelukast sodium intermediate
  • Method for preparing montelukast sodium intermediate

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0030] The preparation of embodiment 1 formula III compound

[0031] 2-(2-(3(S)-chloro-3-(3-(2-(7-chloro-2-quinolyl)-(E)vinyl)phenyl)propyl)phenyl)-2 - Process for the preparation of propanol.

[0032] At room temperature (25-30°C) and under the protection of argon, add 2-(2-(3(R)-hydroxyl-3-(3-(2-(7-chloro-2-quinoline) yl)-(E)vinyl)phenyl)propyl)phenyl)-2-propanol (25.1 g, 55 mmol), DMF (400 mL) and diisopropylethylamine (17.74 g, 137.5 mmol), Stir until completely dissolved. The system was cooled to -10°C with an ice-salt bath, methanesulfonyl chloride (15.6 g, 137.5 mmol) was added dropwise within 30 minutes, and then reacted at this temperature for 10 hours. (TLC or HPLC monitors that the reaction of raw materials is complete); Lithium chloride (11.7g, 275mmol) is added in one go, the ice bath is removed, and the reaction is continued for 14 hours after naturally returning to room temperature. TLC followed the completion of the reaction. Add ice water and 300 mL ethyl...

Embodiment 3

[0042] The preparation of embodiment 3 formula V compound

[0043] 2-(1-((1(R)-(3-(2-(7-chloro-2-quinolyl)-(E)vinyl)phenyl)-3-(2-(2-hydroxy- A preparation method of 2 propyl) phenyl) propylthio) methyl) cyclopropyl) methyl acetate.

[0044] Under the condition of ice water bath (10 ℃) and argon protection, 2-(2-(3(S)-chloro-3-(3-(2-(7-chloro-2-quinolyl)-(E )vinyl)phenyl)propyl)phenyl)-2-propanol (16.1g, 33.8mmol), methyl 1-mercaptomethylcyclopropyl-2-acetate (5.4g, 33.8mmol), cesium carbonate (16.5g, 50.7mmol) was put into DMF (200mL) and the ice-water bath was removed, and the reaction system was reacted at room temperature for 3 hours. The reaction was monitored by TLC. After the reaction was completed, 1000 mL of saturated brine was added to the system, and dried with ethyl acetate (3×50 mL) and anhydrous sodium sulfate. Concentration gave 14.72 g of light yellow oily compound of formula V with a yield of 72.5%.

[0045] ee value = 92%

[0046] LCMS: [M+H] + = 600.2;...

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

No PUM Login to View More

Abstract

The invention relates to a method for preparing montelukast sodium intermediate which is shown as a formula III. The method comprises the following steps of: (1), in a solvent, with the action of alkali, carrying out sulfonylation reaction of secondary hydroxyl in a compound II with a sulfonylation agent; and (2), directly carrying out halogenated reaction of reaction liquid obtained in the step (1) with a halogenated reagent, obtaining the montelukast sodium intermediate, wherein the X is C1, Br, or I. The method for preparing the montelukast sodium intermediate disclosed by the invention is gentle in reaction condition, simplex in product, simple and convenient in purification; in addition, the obtained intermediate is high in optical purity and higher in productivity, and more suitable for industrial production.

Description

technical field [0001] The invention relates to the fields of organic chemistry and medicinal chemistry, in particular to a preparation method of a montelukast sodium intermediate. Background technique [0002] The chemical name of Montelukast Sodium: 2-(1-((1(R)-(3-(2-(7-chloro-2-quinolinyl)-(E)vinyl) Phenyl)-3-(2-(2-hydroxy-2propyl)phenyl)propylthio)methyl)cyclopropyl)sodium acetate, this compound can be used as anti-asthma agent, anti-allergic agent and so on. This compound is at first synthesized by Canadian Merk Frosst company, and discloses the structure of this compound and preparation method thereof in CN1061407A by this company, and its synthetic method is 1 (S)-(3-(2-(7-chloroquinoline- 2-yl)-(E)vinyl)phenyl)-3-(2-(2-hydroxy-2-propyl)phenyl)propanol and 2-(1-(mercaptomethyl)cyclopropyl) Acetate reaction preparation. [0003] [0004] Another synthetic method of montelukast sodium is disclosed in CN1428335A, which is based on 2-(3-(3-(2-(7-chloro-2 quinolinyl)...

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): C07D215/18
Inventor 王天昊余青冬袁斌张范王海龙林志鹏潘龙冈
Owner KAIHUI SCI & TECH DEV SHANGHAI