Preparation method of isoxepac

A technology of isoket acid and phenylacetic acid, applied in the direction of organic chemistry, can solve the problems of non-compliance with energy saving and emission reduction, green, safe production, risk of environmental damage, complex process route, etc., and achieve performance such as improving purity and appearance , reduce energy consumption and discharge of three wastes, and reduce environmental pollution

Active Publication Date: 2012-12-26
HUZHOU HENGYUAN BIOCHEM TECH
View PDF1 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The process is to carry out the condensation reaction of ethyl o-toluate and ethyl p-hydroxyphenylacetate under the action of potassium carbonate and potassium hydroxide, and then use phosphorus pentoxide as a dehydrating agent to cyclize isoket acid. There are certain defects in the process route, which are mainly reflected in the high cost, which leads to the price of imported isoket acid at about 3,000 yuan/kg, and the use of phosphorus pentoxide, which is harmful to the environment and relativel...

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
  • Preparation method of isoxepac
  • Preparation method of isoxepac
  • Preparation method of isoxepac

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] (1) Condensation: Prepare and weigh 10kg of p-hydroxyphenylacetic acid, 9kg of phthalide, and 10 kg of sodium methoxide, dissolve p-hydroxyphenylacetic acid and phthalide with 20kg of DMAC, add sodium methoxide, and then heat to 110°C for 7 hours at a pressure of 2 Pa. , rectification reclaims DMAC solvent, adds the hydrochloric acid solution that HCl content is 9-10wt% and adjusts the pH value to 3-4, crystallizes out 4-(2-carboxybenzyloxy)phenylacetic acid 17.8kg;

[0039] (2) Cycling: Dissolve the obtained 4-(2-carboxybenzyloxy)phenylacetic acid in 15kg of glacial acetic acid, then add 50 parts by weight of polyphosphoric acid, heat to 80°C for 8 hours at a pressure of 2Pa, and then add 5°C The sodium chloride solution cooling crystallization obtains 22kg of isoket acid crude product;

[0040] (3) Purification: Weigh 40 parts by weight of ethyl acetate, heat and dissolve the crude isoket acid, add 1.8kg of activated carbon for decolorization, and blow dry at a temperat...

Embodiment 2

[0046] (1) Condensation: Weigh 8kg of p-hydroxyphenylacetic acid, 6kg of phthalide, and 8kg of sodium methoxide, dissolve the p-hydroxyphenylacetic acid and phthalide with 16kg of DMAC, add the sodium methoxide, and then heat to 80 at a pressure of 0.1Pa. React at ℃ for 3 hours, rectify and recover the DMAC solvent, add a hydrochloric acid solution with an HCl content of 9-10wt% to adjust the pH value to 1, and crystallize 14.5 kg of 4-(2-carboxybenzyloxy)phenylacetic acid;

[0047] (2) Cycling: Dissolve the obtained 4-(2-carboxybenzyloxy)phenylacetic acid in 2kg of glacial acetic acid, then add 3kg of polyphosphoric acid, heat to 30°C for 3h at a pressure of 0.1Pa, then add 2°C Sodium chloride solution cooling crystallization obtains 20kg of isoket acid crude product;

[0048] (3) Purification: Weigh 25kg of ethyl acetate, heat and dissolve the crude isoket acid, add 0.9kg of activated carbon for decolorization, and vacuum dry at a temperature of 30°C to obtain 11.8kg of isok...

Embodiment 3

[0051] (1) Condensation: Weigh 12kg of p-hydroxyphenylacetic acid, 12kg of phthalide, and 12kg of sodium methoxide, dissolve the p-hydroxyphenylacetic acid and phthalide with 25kg of DMAC, add the sodium methoxide, and then heat to 170°C at a pressure of 10Pa React for 10 hours, recover the DMAC solvent by rectification, add a hydrochloric acid solution with an HCl content of 9-10wt% to adjust the pH value to 5, and crystallize 21.6 kg of 4-(2-carboxybenzyloxy)phenylacetic acid;

[0052] (2) Cycling: Dissolve the obtained 4-(2-carboxybenzyloxy)phenylacetic acid with 17kg glacial acetic acid glacial acetic acid, then add 52kg polyphosphoric acid, heat to 100°C under a pressure of 10Pa to react for 12h, then add 20°C The sodium chloride solution cooling crystallization obtains 28kg of isoket acid crude product;

[0053] (3) Purification: Weigh 50kg of ethyl acetate, heat and dissolve the crude isoket acid, add 8.4kg of activated carbon for decolorization, and vacuum dry at a tem...

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 preparation method of isoxepac, belonging to the field of organic matter synthesis. The preparation method sequentially comprises following steps of: 1) condensation: preparing 8-12 parts of p-hydoxyphenylactic acid by weight, 6-12 parts of phthalide by weight and 8-12 parts of sodium methylate, dissolving the p-hydoxyphenylactic acid and the phthalide by using DMAC (dimethylacetamide), adding the sodium methylate, heating the solution to 80-170 DEG C for reaction for 3-10h under pressure of 0.1-10Pa, regulating pH (potential of hydrogen) to 1-5, and conducting crystallization to precipitate 4-(2-carboxybenzyloxy) phenylacetic acid; 2) cyclization: dissolving the 4-(2-carboxybenzyloxy) phenylacetic acid obtained in the step 1 by using glacial acetic acid, adding 3-52 parts of polyphosphoric acid by weight, heating the solution to 30-100 DEG C for reaction for 3-12h under pressure of 0.1-10Pa, and then conducting cooling crystallization to obtain crude isoxepac products; and 3) purification: dissolving the crude isoxepac products by using ethyl acetate and then conducting refining and decolorization to obtain isoxepac products. The preparation method provided by the invention has the advantages of environmental-friendly production, low production cost, high product yield and purity, and short production cycle.

Description

technical field [0001] The invention relates to a preparation method of isoket acid, which belongs to the field of organic compound synthesis. Background technique [0002] Isoket acid is an important intermediate for the synthesis of the new preferred antiallergic drug olopatadine hydrochloride. However, due to the current domestic use of four-step reactions of condensation, hydrolysis, acidification, and cyclization, as well as multiple extraction and recrystallization operations, the traditional process route , the cumbersome traditional process determines the high cost of domestic Isoke acid, and the second hydrolysis reaction of the traditional process is a reversible reaction, resulting in about 8% of unhydrolyzed ester structure impurities will always be brought into the product, and then form impurities Methyl isoketate, the nature of methyl isoketate is very similar to the product, which brings great troubles to the subsequent refining and other post-processing. It ...

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
IPC IPC(8): C07D313/12
Inventor 马维恒谢何青包建辉俞彬
Owner HUZHOU HENGYUAN BIOCHEM TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap