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

Preparation method of 2-R1 valeric acid

A technology of 2-R1 and valeric acid, which is applied in the field of preparation of 2-R1 valeric acid, can solve problems such as harsh conditions and dangerous operation, and achieve the effects of short synthesis route, easy control, and avoiding ultra-high temperature or ultra-low temperature

Pending Publication Date: 2021-07-23
SHANGHAI QINGPING PHARMA CO LTD
View PDF4 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The above process has the following defects: the preparation of lithium diisopropylamide requires low temperature, the conditions are relatively harsh, and the dangerous reagent butyllithium is used, which is more dangerous to operate

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 2-R1 valeric acid
  • Preparation method of 2-R1 valeric acid
  • Preparation method of 2-R1 valeric acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] 1.1 Preparation of methyl 2-cyanovalerate

[0033] Add 720g of methyl cyanoacetate, 1140g of methanol, 714g (0.8eq) equivalent of bromopropane in the reaction flask, raise the temperature to 50 degrees, and add dropwise 784g of a mass concentration of 30% sodium methoxide methanol solution (sodium methoxide 0.6 eq), controlled reaction temperature 50~60 degree, refluxed 1 hour, normal pressure distilled methanol, then reduced pressure distilled methanol to dryness to obtain crude product 1268g. Add 800 ml of isopropyl acetate, beat and filter to remove salt, and wash the obtained isopropyl acetate phase with 500 ml*6 of 5% sodium hydroxide aqueous solution until the methyl cyanoacetate is less than 0.5%, and add 500 ml of concentration to the oil phase Wash once with 1% sulfuric acid aqueous solution, then add 500 milliliters of water and wash once to neutrality, and concentrate the oil phase to dryness to obtain crude product 360g (compound B is 76%, compound C is 20%)...

Embodiment 2

[0042] 2.1 Preparation of methyl 2-cyanovalerate

[0043] Add 720g of methyl cyanoacetate, 1140g of methanol, 892g (1.0eq) equivalent bromopropane in the reaction flask, raise the temperature to 50 degrees, and add dropwise 1041g of a mass concentration of 30% sodium methoxide methanol solution (sodium methoxide 0.8 eq), controlled reaction temperature 50~60 degree, refluxed 1 hour, normal pressure distilled methanol, then reduced pressure distilled methanol to dryness to obtain crude product 1268g. Add 800 ml of isopropyl acetate, beat and filter to remove salt, wash the obtained isopropyl acetate phase with 500 ml*6 of 5% sodium hydroxide aqueous solution until the methyl cyanoacetate is less than 0.5%, add 500 ml of concentration to the oil phase Wash once with 1% sulfuric acid aqueous solution, then add 500 milliliters of water and wash once to neutrality, and concentrate the oil phase to dryness to obtain crude product 360g (compound B is 76%, compound C is 20%), using a ...

Embodiment 3

[0052] 3.1 Preparation of methyl 2-cyanovalerate

[0053] Add 720g of methyl cyanoacetate, 1140g of methanol, 892.5g (1.0eq) of equivalent bromopropane in the reaction flask, heat up to a temperature of 50 degrees, and add dropwise 1306g of a mass concentration of 30% sodium methoxide methanol solution (sodium methoxide 1.0eq), control the reaction temperature at 45-55 degrees, reflux for 1 hour, distill methanol under normal pressure, then distill methanol under reduced pressure to dryness to obtain 1300g of crude product. Add 800 ml of isopropyl acetate, beat and filter to remove salt, wash the obtained isopropyl acetate phase with 500 ml*6 of 5% sodium hydroxide aqueous solution until the methyl cyanoacetate is less than 0.5%, add 500 ml of concentration to the oil phase Wash once with 1% sulfuric acid aqueous solution, then add 500 milliliters of water and wash once to neutrality, and concentrate the oil phase to dryness to obtain 400 g of crude product (compound B is 76%,...

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 preparation method for 2-R1 valeric acid. The preparation method comprises the following steps: step 1, with methyl cyanoacetate as a starting material, adding bromopropane and sodium methoxide, carrying out a catalytic reaction, and conducting purifying to obtain 2-cyanomethyl valerate; step 2, subjecting 2-cyanomethyl valerate to a reaction under the catalysis of iodoalkane and sodium methoxide, and conducting aftertreatment to obtain 2-cyano-2-R1 methyl valerate; step 3, enabling the 2-cyano-2-R1 methyl valerate to undergo a reaction in an aqueous solution of sulfuric acid at 120-160 DEG C for 15-40 hours so as to obtain a mixture of 2-R1 valeric acid and 2-R1 methyl valerate; and step 4, hydrolyzing the mixture by using an aqueous sodium hydroxide solution to obtain 2-R1 sodium valerate and methanol, and conducting acidifying by using inorganic acid to obtain 2-R1 valeric acid. Reagents adopted in the preparation method are relatively common, and the risk of the reagents is relatively low; and reaction conditions are mild, and the temperature is easier to control relatively. The invention develops a purification process of the key intermediate 2-cyanomethyl valerate, and the process flow is simple.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis, in particular to a 2-R 1 Preparation method of valeric acid. Background technique [0002] 2-R 1 Valproic acid is an impurity that is easily produced during the preparation of sodium valproate raw materials, and plays a key role in the detection and control of related substances in the production of sodium valproate raw materials. [0003] In the prior art "Synthesis and Evaluation of Antiallodynic and Anticonvulsant Activity of Novel Amide and Urea Derivatives of Valproic Acid Analogues; J. Med. Chem. 2009, 52, 7236-7248", the preparation of α-alkylated valeric acid and amides is mainly through di Lithium isopropylamide reacts with valeric acid to deprotonate valeric acid α, and then undergoes alkylation reaction with halogenated alkanes to generate carboxylate, and obtains α-alkylated valeric acid after acidification: [0004] [0005] The above-mentioned process has the follow...

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 Applications(China)
IPC IPC(8): C07C51/08C07C253/30C07C253/34C07C53/126C07C255/19
CPCC07C51/08C07C253/30C07C253/34C07C53/126C07C255/19
Inventor 魏正华韦建国顾玉仅景涛
Owner SHANGHAI QINGPING PHARMA CO LTD
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