Method for synthesizing alpha-ketoleucine calcium

A technology of ketoleucine calcium and a synthesis method, which is applied in the field of pharmaceutical raw materials, can solve the problems of difficult hydrolysis of 5-benzylidene hydantoin, short reaction steps, and long reaction time, and achieve easy control of the reaction, easy hydrolysis, The effect of small investment in equipment

Inactive Publication Date: 2011-04-27
ZHEJIANG NHU CO LTD
View PDF3 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This synthetic route is relatively simple, and the reaction steps are short, but the hydrolysis of 5-benzylidene hydantoin is difficult, requires a large amount of lye, and the reaction time is long, the conditions are harsh, and the hydrolysis yield is low

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 synthesizing alpha-ketoleucine calcium
  • Method for synthesizing alpha-ketoleucine calcium
  • Method for synthesizing alpha-ketoleucine calcium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Example 1: Preparation of 4-isobutylene-2-methyldihydrooxazolone

[0045] Put 37.5g (0.5mol) of pharmaceutical grade glycine and 50.5g (0.5mol) of triethylamine into a 500ml three-necked flask equipped with mechanical stirring, thermometer, and reflux condenser, stir evenly, and add dropwise at 50°C while stirring and cooling 127.5g (1.25mol) of acetic anhydride, the dropwise addition of acetic anhydride is completed, and the reaction is stirred at 40-50°C for 1 hour, then 36g (0.5mol) of isobutyraldehyde is added dropwise in 15 minutes, and the temperature is raised to 60-65°C for reaction After 3 hours, heat up to 90°C in 3 hours, and continue to react at 90-100°C for 3 hours until the peak of isobutyraldehyde disappears. After the reaction is completed, the mixture of isobutyraldehyde, acetic anhydride, acetic acid, and triethylamine is distilled off under reduced pressure. After distillation, it can be used in the next batch of reactions. The residue is cooled to a ...

Embodiment 2-6

[0046] Example 2-6: Preparation of 4-isobutylidene-2-methyldihydrooxazolone under the same conditions as Example 1 except that different catalysts are used.

[0047]

Embodiment 7

[0048] Example 7: Preparation of 4-isobutylene-2-methyldihydrooxazolone

[0049] In a 500ml three-necked flask equipped with a mechanical stirrer, a thermometer, and a reflux condenser, put 37.5g (0.5mol) of pharmaceutical grade glycine and 33.3g (0.25mol) of N,N'-dimethylpiperazine, stir well, and cool Add 127.5g (1.25mol) of acetic anhydride dropwise under control at 50°C. After the dropwise addition of acetic anhydride is complete, stir and react at 40-50°C for 1 hour, then add 36g (0.5mol) of isobutyraldehyde dropwise in 15 minutes. Raise the temperature to 60-65°C for 3 hours, then raise the temperature to 90°C for 3 hours, continue to react at 90-100°C for 3 hours until the peak of isobutyraldehyde disappears, and the reaction is completed. The mixture was dissolved by adding 500 mL of toluene to the residue, washed twice by adding 100 mL of water each time, the toluene solution was evaporated to dryness under reduced pressure, and cooled to obtain a solid of 4-isobutyli...

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 method for synthesizing alpha-ketoleucine calcium which serves as a medicinal raw material. In the conventional methods, certain methods are complex to operate, and have low yield, hydrogen peroxide is used in the oxidation process and safe production is not facilitated; and certain methods have long reaction time, severe conditions and low hydrolysis yield. The method comprises the following preparation steps of: performing catalytic cyclization reaction on glycine, iso-butyraldehyde, acetic anhydride and an organic base catalyst which serve as raw materials by a one-pot method to obtain 4-isobutylidene-2-methyl dihydro oxazolone; and performing open-loop hydrolysis reaction on the 4-isobutylidene-2-methyl dihydro oxazolone and calcium hydroxide in a pipeline reactor to obtain the alpha-ketoleucine calcium. The one-pot method is adopted in the cyclization reaction; the method has the advantages of small equipment investment, low operation cost and no wastewater and an organic amine catalyst is easy to recycle; and continuous feeding and discharging are performed by a pipeline reaction in the hydrolysis reaction, so continuous production is realized, and the efficiency is high.

Description

technical field [0001] The invention relates to a pharmaceutical raw material, in particular to a method for synthesizing α-ketoleucine calcium. Background technique [0002] Calcium α-ketoleucine is the main ingredient of compound α-ketoacid tablets. Compound α-ketoacid tablets are used for the treatment of uremia, providing essential amino acids for patients with kidney disease and minimizing the intake of amino nitrogen. Keto or hydroxyamino acids do not contain amino groups themselves, and use the nitrogen of non-essential amino acids to convert them into amino acids, thereby reducing urea synthesis and reducing the accumulation of uremic toxic products. [0003] The structural formula of alpha-ketoleucine calcium is as follows: [0004] [0005] At present, there are mainly the following synthetic methods for α-ketoleucine calcium: [0006] (1) J.Org.Chem.1963, 28(11): 3088-92, taking ethyl cyanoacetate and isobutyraldehyde as starting materials, and reacting with...

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): C07C59/185C07C51/09
CPCY02P20/584
Inventor 钱洪胜鲁国彬吕叔敏姜延平杨芝
Owner ZHEJIANG NHU CO LTD
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