Method for synthesizing 1,3-dibenzyl imidazoline-2-keto-cis-4,5-dicarboxylic acid

A technology of dibenzyl imidazoline and dicarboxylic acid, applied in the direction of organic chemistry, can solve the problems of harsh labor protection conditions, restrictions on phosgene transportation and storage, cumbersome recovery of excess benzylamine, etc., to improve the production environment, impurity Less, less expensive effects

Active Publication Date: 2011-10-19
DAFENG HEGNO PHARMA +1
View PDF12 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The above-mentioned technology has the following problems: 1. the preparation of the raw material cis-2,3-dibenzylaminosuccinic acid is all based on cis-2,3-dihalogenated succinic acid as a raw material, and a large excess of benzylamine needs to be used to react, And the recovery of excess benzylamine is cumbersome (see U.S. Patent US2486232, Japanese Patent JP2006232742), which leads to high cost of the above synthesis technology
② As a cyclizing agent, phosgene has strict labor protection requirements, and the transportation and storage of a large amount of phosgene are restricted
3. phenyl chloroformate is as cyclizing agent, and raw material is e

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 1,3-dibenzyl imidazoline-2-keto-cis-4,5-dicarboxylic acid
  • Method for synthesizing 1,3-dibenzyl imidazoline-2-keto-cis-4,5-dicarboxylic acid
  • Method for synthesizing 1,3-dibenzyl imidazoline-2-keto-cis-4,5-dicarboxylic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] 1. Synthesis of dibenzylurea

[0036] In a 250ml four-neck flask, add 20g (333.00mmol) of urea, 85.64g (799.20mmol) of benzylamine, 2.22g (16.65mmol) of aluminum chloride and 100ml of DMF, and heat up to 100°C after argon replacement, and react for 30 minutes . The reaction solution was cooled to 20° C., then poured into a beaker containing 50 g of crushed ice, and stirred for 30 minutes. Suction filtration, washing with 2*20ml of water, and vacuum drying yielded 76.18g of dibenzylurea (molar yield: 95.2%), white solid, melting point: 167.2-168.3°C.

[0037] 1 H-NMR (DMSO-d 6 , 400MHz): δ 4.46 (d, 2H), 4.75 (dd, 4H), 7.29-7.40 (m, 10H). 13 C-NMR (DMSO-d 6 ): δ158.8, 139.3, 128.8, 127.4, 44.5.

[0038] 2. Synthesis of target product 1,3-dibenzyl imidazolin-2-one-cis-4,5-dicarboxylic acid

[0039]In a 500ml four-necked flask, 20g (83.23mmol) of dibenzylurea, 22.96g (83.23mmol) of cis-2,3-dibromosuccinic acid and 160g of acetic acid were added. After argon replacem...

Embodiment 2

[0049] The only difference between this example and Example 1 is that "22.96g (83.23mmol) cis-2,3-dibromosuccinic acid" is replaced by "15.56g (83.23mmol) cis-2,3-dibromosuccinic acid" Chlorobutacic acid ", all the other contents are identical with those described in Example 1.

[0050] According to the HPLC purity analysis conditions described in Example 1, the analysis shows that the HPLC purity of the target product obtained by the method of this example is 99.73%.

Embodiment 3

[0052] The difference between this embodiment and Example 1 is only: "2.22g (16.65mmol) aluminum chloride" is replaced by "2.36g (16.65mmol) boron trifluoride ether", and the rest of the content is the same as in Example 1 Same as described.

[0053] According to the HPLC purity analysis conditions described in Example 1, the analysis shows that the HPLC purity of the target product obtained by the method of this example is 99.62%.

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

PropertyMeasurementUnit
Melting pointaaaaaaaaaa
Login to view more

Abstract

The invention discloses a method for synthesizing 1,3-dibenzyl imidazoline-2-keto-cis-4,5-dicarboxylic acid, which comprises the following step b or step a to step b in a synthesis route: step a, reacting carbamide (II) with benzylamine (III), thus obtaining bibenzyl-ure (IV); and the step b, reacting the bibenzyl-ure (IV) with cis-2,3-dihalogenated succinic acid (V), thus obtaining the 1,3-dibenzyl imidazoline-2-keto-cis-4,5-dicarboxylic acid. The synthesizing method has the advantages of mild reaction conditions, high safety, simplicity and convenience for operation, easiness in purification processing of a final product, capability of leading HPLC (High Performance Liquid Chromatography) purity of a target product to be exceeded 99.5 percent, stable quality, easiness in obtaining raw materials, low price, high total recovery and the like, so that the total cost is greatly lowered, and the method is suitable for large-scale industrialization production requirements.

Description

technical field [0001] The invention relates to a new synthesis method of 1,3-dibenzylimidazolin-2-one-cis-4,5-dicarboxylic acid, which belongs to the technical field of chemical drug synthesis. Background technique [0002] 1,3-Dibenzylimidazolin-2-one-cis-4,5-dicarboxylic acid is a key intermediate for the preparation of biotin (vitamin H, coenzyme R). U.S. Patent No. 4,659,837 and U.S. Patent No. 5,151,525 disclose cis-2,3-dibenzylaminosuccinic acid as a raw material, and under alkaline conditions, feed phosgene to synthesize the compound; European Patent EP1127879A1 discloses cis-2,3- Dibenzylaminosuccinic acid is used as a raw material, and under alkaline conditions, the compound is synthesized using phenyl chloroformate as a cyclizing agent; European Patent EP1081139A2 and Chinese Patents CN1356320A and CN1434039A all disclose cis-2,3-dibenzylamine The compound was synthesized using triphosgene as a cyclizing agent under alkaline conditions using succinic acid as a ra...

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): C07D233/32
Inventor 刘德铭鲁向阳徐光明
Owner DAFENG HEGNO PHARMA
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