Supercharge Your Innovation With Domain-Expert AI Agents!

Synthesis method of 1-hydroxycyclopropane carboxylic acid and 1-hydroxycyclopropane carboxylate

A technology of hydroxycyclopropane carboxylic acid and synthesis method, which is applied in the direction of carboxylate preparation, carboxylate/lactone preparation, separation/purification of carboxylic acid compounds, etc., and can solve large pollution, low yield and harsh reaction conditions and other problems, to achieve the effects of mild and controllable reaction conditions, simple post-processing, and strong operability

Active Publication Date: 2020-03-06
上海添泽生物医药有限公司
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The purpose of the present invention is to provide a synthetic method of 1-hydroxycyclopropanecarboxylic acid and carboxylic acid ester, aiming to solve the problem of harsh reaction conditions and low yield in the synthetic method of 1-hydroxycyclopropanecarboxylic acid and its derivatives in the prior art. Low rate and high pollution technical problems

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
  • Synthesis method of 1-hydroxycyclopropane carboxylic acid and 1-hydroxycyclopropane carboxylate
  • Synthesis method of 1-hydroxycyclopropane carboxylic acid and 1-hydroxycyclopropane carboxylate
  • Synthesis method of 1-hydroxycyclopropane carboxylic acid and 1-hydroxycyclopropane carboxylate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] (1) Synthesis of Compound 2

[0036]

[0037] Dissolve compound 1 (3.41g, 29.6mmol, 1.0eq) in 40ml of sulfuric acid aqueous solution A (prepared by adding 1.62mL of 98% concentrated sulfuric acid to water, the molar equivalent of sulfuric acid is 1.0eq), and cool down to 0-5°C in an ice bath , Add 10ml of sodium nitrite (2.25g, 32.6mmol, 1.1eq) aqueous solution to the reaction solution, and stir at room temperature for 1 hour. Then the above reaction solution was added dropwise to refluxed 100ml sulfuric acid aqueous solution B (prepared by adding 1.62mL of 98% concentrated sulfuric acid into water, the molar equivalent of sulfuric acid was 1.0eq). After the dropwise addition was completed, the heating was stopped and cooled to room temperature. After the reaction was detected by TLC, ethyl acetate (3*100mL) was extracted three times, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, and the organic phase was concentrated to obtain c...

Embodiment 2

[0044] (1) Synthesis of Compound 2

[0045] Compound 1 (1200.0 g, 10.4 mol, 1.0 eq) was dissolved in 12 L of sulfuric acid aqueous solution (prepared by adding 0.57 L of 98% concentrated sulfuric acid into water, the molar equivalent of sulfuric acid was 1.0 eq), cooled to 0-5 °C in an ice bath, and 3.5 L of sodium nitrite (793.5 g, 11.5 mol, 1.1 eq) aqueous solution was added to the reaction liquid, and stirred at room temperature for 1 hour. Then the above reaction solution was added dropwise to 35L of refluxing sulfuric acid aqueous solution B (prepared by adding 0.57L of 98% concentrated sulfuric acid into water, and the molar equivalent of sulfuric acid was 1.0eq). After the addition was completed, stop heating, cool to room temperature, and detect by TLC After the reaction was completed, ethyl acetate (3*12L) was extracted three times, the organic phases were combined, dried with anhydrous magnesium sulfate, filtered, and the organic phase was concentrated to obtain comp...

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 synthesis method of 1-hydroxycyclopropane carboxylic acid and 1-hydroxycyclopropane carboxylate. The method includes: taking 1-aminocyclopropyl formate as the raw material for reaction under the catalysis of sodium nitrite and sulfuric acid to generate 1-hydroxycyclopropyl formate; and removing an ester protecting group from the 1-hydroxycyclopropyl formate to obtain 1-hydroxycyclopropane carboxylic acid. The method provided by the invention adopts the commercially available methyl 1-aminocyclopropyl formate as the raw material, carries out two-step reaction to generate 1-hydroxycyclopropane carboxylic acid, and optimizes the reaction process conditions to make the total yield reach 60%-70%. According to the method, the reaction conditions are mild and controllable, the post-treatment is simple, and the high-purity target product can be obtained through simple extraction and concentration; the method has strong operability, and is suitable for industrial enlarged production.

Description

technical field [0001] The invention relates to the technical field of preparation of pharmaceutical intermediates, in particular to a method for synthesizing 1-hydroxycyclopropane carboxylic acid and carboxylic acid ester. Background technique [0002] Because many compounds containing cyclopropane substructural units have good biological activity, cyclopropane has a very wide range of applications in drug design, such as the design of many heterocyclic drugs, peptide biopharmaceuticals, and pesticides widely used in agriculture. Molecules have cyclopropane structural units. In the development of base enzyme inhibitors in recent years, the structure of hydroxycyclopropane has been used frequently. However, the scale-up production of 1-hydroxycyclopropanecarboxylic acid and its derivatives is still a difficult problem. [0003] The existing synthetic methods are: [0004] [0005] In the first step of this route, metal sodium is used as alkali, and in the second step, ...

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): C07C51/09C07C51/48C07C62/02C07C67/31C07C69/743
CPCC07C51/09C07C51/48C07C67/31C07C2601/02C07C62/02C07C69/743Y02P20/55
Inventor 李进飞
Owner 上海添泽生物医药有限公司
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com