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

Preparation method of 2-(1-adamantly) glyoxylic acid

A technology of adamantyl and adamantane carboxylic acid is applied in the preparation of saxagliptin intermediates and the field of preparation of saxagliptin intermediates 2-(1-adamantyl)glyoxylic acid, which can solve the complicated synthesis steps , large product loss, low yield and other problems, to achieve the effect of simple post-processing operation, short reaction time, high yield and purity

Inactive Publication Date: 2013-09-18
SUZHOU UUGENE BIOPHARMA
View PDF3 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Although the above method has finally produced 2-(1-adamantyl)glyoxylic acid, the synthesis steps of this method are cumbersome, and both the dangerous substance thionyl chloride which is harmful to the human body and the more expensive liquid active Trimethylsilane cyanide, and in the above method, the cyano group on the 1-adamantanecarbonitrile is first hydrolyzed into an amide, and then the amide is hydrolyzed into a carboxylic acid to obtain 2-(1-adamantyl)glyoxylic acid, The product loss during the reaction is large, so that the yield of the synthesis of 2-(1-adamantyl)glyoxylic acid 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
  • Preparation method of 2-(1-adamantly) glyoxylic acid
  • Preparation method of 2-(1-adamantly) glyoxylic acid
  • Preparation method of 2-(1-adamantly) glyoxylic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Substitution reaction: Add 50 g of 1-adamantanecarboxylic acid into a reaction flask and dissolve in 300 mL of dichloromethane, and stir until all 1-adamantanecarboxylic acid is dissolved to obtain a reaction solution. The reaction liquid was cooled to 0° C., and 41.3 g of sulfuryl chloride was added to the reaction liquid. After the addition, the reaction liquid was heated to 25° C. and stirred for 2 hours until the reaction was complete. The reaction solution after the complete reaction was directly concentrated to obtain 55.1 g of 1-adamantanecarbonyl chloride with a yield of 100%.

[0034] Cyanide reaction: Add 55.1g of 1-adamantanecarbonyl chloride prepared above into the reaction flask, dissolve in 100mL of methyl tert-butyl ether and 20mL of N,N-dimethylformamide, stir until 1-adamantanecarbonyl chloride All dissolved in the reaction solution. Add 14.9 g of sodium cyanide in batches to the reaction solution, and continue stirring for 5 hours after the addition i...

Embodiment 2

[0037] Substitution reaction: add 45.1g of 1-adamantanecarboxylic acid into the reaction flask and dissolve in 300mL of chloroform, and stir until the 1-adamantanecarboxylic acid is completely dissolved to obtain a reaction solution. The reaction liquid was cooled to -2°C, and 35.1 g of oxalyl chloride was added to the reaction liquid. After the addition, the reaction liquid was heated to 22°C and stirred for 1.5 hours until the reaction was complete. The reaction solution after the complete reaction was directly concentrated to obtain 49.5 g of 1-adamantanecarbonyl chloride, and the yield was 100%.

[0038] Cyanogenation reaction: Add 49.5g of 1-adamantanecarbonyl chloride prepared above into the reaction flask, dissolve in 100mL ether and 20mL N,N-dimethylacetamide, stir until 1-adamantanecarbonyl chloride is completely dissolved to obtain a reaction solution . Add 17.6 g of potassium cyanide in batches to the reaction solution, and continue stirring for 5 hours after the a...

Embodiment 3

[0041] Substitution reaction: add 63.1g of 1-adamantanecarboxylic acid into the reaction flask and dissolve in 350mL of 1,2-dichloroethane, stir until all of the 1-adamantanecarboxylic acid is dissolved to obtain a reaction solution. The reaction solution was cooled to 0° C., and 63.2 g of phosphorus oxychloride was added to the reaction solution. After the addition, the reaction solution was heated to 20° C. and stirred for 2.5 hours until the reaction was complete. The reaction solution after the completion of the reaction was directly concentrated to obtain 69.5 g of 1-adamantanecarbonyl chloride, with a yield of 100%.

[0042] Cyanide reaction: Add 69.5g of 1-adamantanecarbonyl chloride prepared above into the reaction flask, dissolve in 120mL of isopropyl ether and 30mL of N,N-dimethylformamide, and stir until 1-adamantanecarbonyl chloride is completely dissolved to obtain The reaction solution. Add 68.9 g of cuprous cyanide in batches to the reaction solution, and conti...

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
Wavelengthaaaaaaaaaa
Login to View More

Abstract

The invention relates to a preparation method of saxagliptin intermediate 2-(1-adamantly) glyoxylic acid, which belongs to the technical field of pharmaceutical synthesis and is used for solving the problems that the reaction steps of the preparation method of the 2-(1-adamantly) glyoxylic acid in the prior art are tedious, dangerous reagent is used in the reaction, the yield is low and the like. The preparation method comprises the following steps of: substitution reaction, wherein substitution reaction is carried out on 1- adamantly to obtain 1- adamantly formyl chloride; cyaniding reaction, wherein cyaniding reaction is carried out on 1- adamantly formyl chloride under the action of cyaniding agent to obtain 1- adamantly formyl nitrile; and cyano-group hydrolysis reaction, wherein the cyano-group hydrolysis reaction is carried out on the 1- adamantly formyl nitrile under the alkaline system to obtain 2-(1-adamantly) glyoxylic acid. According to the preparation method of the 2-(1-adamantly) glyoxylic acid disclosed by the invention, the using reagent is cheap and easily available, green and environment-friendly; the reaction conditions are gentle; the reaction time is short; the post-treatment operation is simple; the conversation rate, the yield and the purity are high; the product quality is good.

Description

technical field [0001] The invention relates to a preparation method of a saxagliptin intermediate, in particular to a preparation method of a saxagliptin intermediate 2-(1-adamantyl)glyoxylic acid, which belongs to the technical field of pharmaceutical synthesis. Background technique [0002] Saxagliptin, trade name Onglyza, chemical name (1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxytricyclo[3.3.1.13,7]decane Alkyl-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile, jointly developed by Bristol-Myers Squibb Company and Astra Zeneca Company, approved by FDA in July 2009, is A highly selective and reversible competitive inhibitor of dipeptidyl peptidase IV (DPP-IV), which is well tolerated and does not cause obesity, and is clinically used for the treatment of type 2 diabetes. [0003] 2-(1-adamantyl)glyoxylic acid is an important intermediate in the synthesis of saxagliptin. 2-(1-adamantyl)glyoxylic acid, CAS registration number: 16091-98-8, melting point 101-103°C, its struc...

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): C07C59/80C07C51/08
CPCY02P20/582
Inventor 李志强王伸勇王晓俊胡隽恺
Owner SUZHOU UUGENE BIOPHARMA
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