Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Synthetic method of fexofenadine intermediate

A technology of fexofenadine and a synthesis method, which is applied in the field of organic chemical synthesis, can solve the problems of long reaction time, difficult to remove, and high cost, and achieves the effects of convenient operation, novel reaction route and high yield

Inactive Publication Date: 2012-09-12
ZHEJIANG QIMING PHARMA +1
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The disadvantage of this method is to obtain 4-(4-chlorobutyryl)-α by Friedel-Crafts reaction, while α-dimethylphenylacetic acid methyl ester will produce a certain proportion of meta-isomers-3-(4- Chlorobutyryl)-α, α-dimethylphenylacetic acid methyl ester, the molar ratio of p-position and meta-position is about 1:1, the physical and chemical properties of meta-position isomer are very similar to para-position target object, it is difficult to Its removal; the condensation reaction with AZA needs to be refluxed in toluene for 72 hours, the reaction time is extremely long, and the yield is very low (or no yield data)
In addition, since there is no large-scale manufacturer of AZA in my country, the synthesis of fexofenadine and its intermediates has long been dependent on imports, and the cost is relatively high

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
  • Synthetic method of fexofenadine intermediate
  • Synthetic method of fexofenadine intermediate
  • Synthetic method of fexofenadine intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] (1) Dissolve 28.3 g (0.10 mol) of 4-(4-chlorobutyryl)-α, α-dimethylphenylacetic acid methyl ester in 100 ml of 4-methyl-2-pentanone, stir, and add 4-cyano Base piperidine 11.0g (0.10mol), potassium carbonate 34.5g (0.25mol), catalyst potassium iodide 0.2g, be warming up to 90 ℃, reflux after 4 hours, filter, filter out catalyst and inorganic salt potassium carbonate, and the filtrate is concentrated under reduced pressure to Dry, add 100ml of toluene, 100ml of water, separate the layers, extract the water layer with toluene (50ml*2), combine the organic layers, dry, concentrate to 1 / 3 volume, cool and a white solid precipitates, filter, and dry the solid at 70°C , to obtain 32.1 g of 2-(4-(4-(4-cyano-1-piperidinyl)butyryl)phenyl)-2-methyl-propionic acid methyl ester, yield 90.1%.

[0040] (2) Slowly put 5.0 g (0.22 mol) of sodium metal into 100 ml of xylene in batches, pass through nitrogen protection, heat up to 70 ° C, start stirring, and continuously drop 100 ml of x...

Embodiment 2

[0042] (1) Dissolve 28.3 g (0.1 mol) of 4-(4-chlorobutyryl)-α, α-methyl phenylacetate in 100 ml of toluene, stir, and add 11.0 g (0.1 mol) of 4-cyanopiperidine ), potassium carbonate 34.5g (0.25mol), catalyst potassium iodide 0.2g, be warming up to 90 ℃, after refluxing for 10 hours, filter, filter out catalyst and inorganic salt potassium carbonate, add water 100ml to filtrate, separate layers, water layer and toluene (50ml*2) extraction, combined organic layers, dried, concentrated to 1 / 3 volume, cooled, a white solid precipitated, filtered, and the solid was dried at 70°C to obtain 30.8g 2-(4-(4-(4-cyano Base-1-piperidinyl)butyryl)phenyl)-2-methyl-propionic acid methyl ester, the yield was 86.5%.

[0043] (2) Slowly put 5.0g (0.22mol) of sodium metal into 100ml of xylene in batches, pass through nitrogen protection, heat up to 70°C, start stirring, and continuously drop 100ml of xylene and 16.5g of benzophenone (0.09 mol) clarified solution, dripped in 2 hours. Heat up to...

Embodiment 3

[0045] (1) Except replacing 0.2g potassium iodide with 0.2g sodium iodide, other steps are the same as in Example 1 to obtain 31.0g 2-(4-(4-(4-cyano-1-piperidinyl)butyryl)phenyl )-2-methyl-propionic acid methyl ester, yield 87.0%.

[0046] (2) Except replacing 0.22mol sodium metal with 0.18mol sodium metal, other steps are the same as in Example 1 to obtain 2-[4-[4-[4-(hydroxybenzhydryl)-1-piperidinyl]-1 -Oxobutyl]phenyl]-2,2-dimethyl acetate 39.2g, content 98%, yield 84.9%. The proton nuclear magnetic spectrum data of product and 2-[4-[4-[4-(hydroxybenzhydryl)-1-piperidinyl]-1-oxobutyl]phenyl]-2,2-dimethyl The methyl acetate reference substance is basically the same, and the structure is confirmed.

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 discloses a synthetic method of a fexofenadine intermediate 2-[4-[4-[4-(Hydroxy diphenylmethyl)-1-piperidyl]-1-oxobutyl]phenyl]-2,2-dimethyl acetate, which comprises the following steps: carrying out condensation reaction on 4-(4-chlorobu-tyrylcyclohexanone)-alpha, alpha-dimethyl phenylacetate and 4-cyanoacrylate piperidine to obtain 2-[4-[4-(4-cyanoacrylate-1-piperidyl)]butyryl]phenyl]-2-methyl-propionate shown in a formula V and carrying out coupling reaction with benzophenone to obtain the 2-[4-[4-(Hydroxy diphenylmethyl)-1-piperidyl]-1-oxobutyl]phenyl]-2,2-dimethyl acetate shown in a formula VI. The synthetic method has the advantages of simple process, convenience in operation and higher yield and is a route suitable for industrial production, thereby having wide application prospect.

Description

technical field [0001] The invention relates to the field of organic chemical synthesis, in particular to a fexofenadine key intermediate-2-[4-[4-[4-(hydroxybenzhydryl)-1-piperidinyl]-1-oxo Substitute butyl] phenyl] -2, the synthetic method of 2-dimethyl acetate. Background technique [0002] 2-[4-[4-[4-(Hydroxybenzhydryl)-1-piperidinyl]-1-oxobutyl]phenyl]-2,2-dimethylacetate, its structural formula as follows: [0003] wherein R is an alkyl group. [0004] 2-[4-[4-[4-(Hydroxybenzhydryl)-1-piperidinyl]-1-oxobutyl]phenyl]-2,2-dimethylacetate is a An important pharmaceutical intermediate, the antihistamine fexofenadine can be obtained through two-step reactions of hydrolysis and reduction. Specifically, it can be found in the US Pat. Benzyl)-1-piperidinyl]-1-oxobutyl]phenyl]-2,2-dimethyl acetate as raw material through hydrolysis, in NaBH 4 and ethanol (EtOH) in the presence of reduction to prepare the method for fexofenadine. [0005] Fexofenadine (fexofenadine), chem...

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): C07D211/22
Inventor 卢小逸吴文良张启明董道敏邵琦王诚
Owner ZHEJIANG QIMING PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com