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

Preparation method of 3-oxobutanoic acid-2-nitrile ethyl ester and homologues thereof

A technology of oxobutyric acid and ethyl nitrile, which is applied in the preparation of carboxylic acid nitrile, the preparation of organic compounds, chemical instruments and methods, etc., can solve the problems of flammability and explosion, easy self-polymerization, unfavorable storage and transportation, etc. Achieve the effects of avoiding harsh reaction conditions, improving operational safety, and simple raw materials

Inactive Publication Date: 2011-12-21
SICHUAN UNIV
View PDF5 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the reaction is a quantitative reaction, the raw material diketene is flammable and explosive, has high toxicity and lachrymatory effect, and at the same time it is easy to self-polymerize and emit a large amount of carbon monoxide to cause an explosion, which is not conducive to storage and transportation.
Considering the properties of diketene, it is difficult to make this step reaction industrialized production

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] After mixing 100 g of compound 2, 71 g of compound 3, and 1 L of cyclohexane, 10% triphenylphosphine was added to react at 130°C under reflux, and TLC monitoring was performed. The reaction was completed, concentrated, and the residue was subjected to column chromatography on silica gel (60-120 mesh) with an eluent ratio of ethyl acetate:cyclohexane 2:8 to obtain 86.8 g of the pure target compound with a yield of 65%.

Embodiment 2

[0023] 50 g of compound 2, 50 g of compound 3, and 500 ml of toluene were mixed, 5% I2 was added, an appropriate amount of molecular sieve was added, and the reaction was refluxed at 130 °C, and monitored by TLC. After the reaction was completed, 50 ml of 1 mol sodium thiosulfate solution was added, stirred for a while, and the organic layer was separated. After the organic layer was extracted with water, it was concentrated to the minimum volume to obtain a brown oil. Under reduced pressure distillation, the product was distilled at 127-129 ° C to obtain 37 g of a clear, transparent and colorless liquid with a yield of 55.4%.

Embodiment 3

[0025] 75 g of compound 2, 70 g of compound 3, and 1 L of cyclohexane were mixed, 5% I2 was added, and the reaction was refluxed at 130 °C, and monitored by TLC. After the reaction was completed, 75 ml of 1N sodium thiosulfate solution was added, stirred for a while, and the organic layer was separated. After the organic layer was extracted with water, it was concentrated to a minimum volume to obtain a brown oil. Under reduced pressure distillation, the product was evaporated at 127-129 ° C to obtain 45 g of a clear, transparent and colorless liquid with a yield of 45%.

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 provides a method for preparing 3-oxobutanoic acid-2-nitrile ethyl ester and its homologues by using acetoacetate as a raw material through transesterification reaction catalyzed by Lewis acid. Under Lewis acid catalysis, acetoacetate undergoes transesterification reaction with hydroxyethyl, propylene, butyl, pentamyl, hexyl or heptanonitrile to generate the target compound, and then the target product is obtained by vacuum distillation. The method can avoid the use of extremely active, flammable and explosive diketene reagents, avoid harsh reaction conditions, unsafe operation and other problems, and can adapt to industrial production requirements. Not only the raw materials are simple and easy to obtain, but also the operation safety is greatly improved, and has great industrial application value.

Description

technical field [0001] The invention relates to a process method for synthesizing 3-oxobutyric acid-2-carbonitrile ethyl ester, a key intermediate of clevidipine butyrate, and its homologues by using Lewis acid as a catalyst. Background technique [0002] 3-Oxobutyric acid-2-carbonitrile ethyl ester is an important intermediate for the preparation of hypertension drug clevidipine butyrate. At present, there are many synthesis of clevidipine butyrate. Although the synthetic routes are different, the use of the intermediate β-ketoester 1 as the relevant raw material cannot be avoided. There are few reports on the synthesis of the key intermediate 3-oxobutyric acid-2-carbonitrile ethyl ester in existing patents. [0003] Among the existing reports, JP5262696 reports that diketene is reacted with 3-hydroxypropionitrile to obtain 3-oxobutyric acid-2-nitrile ethyl ester. Although the reaction is a quantitative reaction, the raw material diketene is flammable and explosive, has h...

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): C07C253/30C07C255/14C07C255/16
Inventor 吴勇海俐陈雷宋婧婧李晓岑
Owner SICHUAN UNIV
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