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

The preparation method of (s)-3-hydroxyadamantane glycine

A technology of adamantane glycine and adamantane, which is applied in the field of preparation of -3-hydroxyadamantane glycine, can solve the problems of low enantioselectivity, high cost of biocatalytic enzymes, unsuitable for domestic production and the like, and achieves enantiomeric The effect of high bioselectivity, pollution-free industrial production, and easy industrial production

Inactive Publication Date: 2016-08-24
JIAXING UNIV
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although the selectivity of PDH / FDH enzymes is relatively high, the method of biological enzyme catalysis requires high-cost biocatalytic enzymes, which is not suitable for domestic production. Finding economical and practical chiral catalysts is the key to the synthesis of this substance
[0006] In addition, the chemical synthesis methods are as follows: (1) using adamantanecarboxylic acid as the starting material, through the oxidation of hydroxy acid, substitution, decarboxylation 3-step reaction to prepare adamantane methyl ketone, and then oxidize to obtain 2-(3- Hydroxy-1-adamantyl)-2-1-oxoacetic acid, reacted with hydroxylammonium hydrochloride to obtain 2-(3-hydroxy-1-adamantyl)-2-glyoxylate oxime, and reduced to obtain 3-hydroxy- 1-adamantane glycine; (2) tert-butyl 2-(3-hydroxyl-1-adamantyl)-2-oxoacetate undergoes asymmetric reduction of amino group with benzylamine under the action of chiral square amido alcohol catalyst 3-Hydroxy-1-adamantyl-D-glycine is obtained after hydrolysis of the ester; but the above-mentioned synthetic method either has more synthesis steps, or the reaction yield is low, and the enantioselectivity is not high, so it is necessary to develop and prepare Process route with simple process, high product yield and high purity

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
  • The preparation method of (s)-3-hydroxyadamantane glycine
  • The preparation method of (s)-3-hydroxyadamantane glycine
  • The preparation method of (s)-3-hydroxyadamantane glycine

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0021] Preparation of quinoline type alkaloid cinchonine sulfonate derivatives:

[0022] In a 250ml two-necked flask, add cinchonine (3.1g) and solvent chloroform (50ml) where R is methyl, stir to dissolve and cool to below 10°C with ice water, then slowly add chlorosulfonic acid (1.2g) in chloroform Solution, reaction control below room temperature, stirring reaction, TLC monitoring reaction is complete, add sodium bicarbonate (3g) aqueous solution, stir for 3 hours, evaporate part of solvent under reduced pressure, then add sodium bicarbonate solution and carry out liquid separation, collect water phase , part of the water was distilled off under reduced pressure, cooled and crystallized to obtain 1.3 g of the product. MS(EI): 411.14.

[0023] 1 H NMR: 1.13-1.50(2H), 1.69-1.78(3H), 2.16(1H), 2.60(1H), 2.62(1H), 3.05(1H), 3.11(1H), 3.51(1H), 3.60(3H ), 3.92(1H), 4.90(1H), 4.95(1H), 5.49(1H), 5.72(1H), 7.44(1H), 7.46(1H), 7.56(1H), 7.92(1H), 8.45(1H ).

[0024] Compounds ...

Embodiment 1

[0026] Add 2-(3-hydroxyl-1-adamantane)-2-oxoacetic acid (20.0g, 89mmol) and quinoline alkaloid cinchonine sulfonate (0.6g) successively in a 250ml two-necked flask , 60g of 5% aqueous sodium hydroxide solution and p-hydroxybenzylamine (15.4g, 0.125mol) mixture was heated up to 40°C, concentrated after 12 hours of reaction, reacted with concentrated hydrochloric acid to adjust the pH value of the reaction solution to about 6, and then frozen to -5°C The product was precipitated left and right, and 19.69 g of the product was obtained by freeze-drying after suction filtration, the ee value was 97.1%, and the yield was 98.2%.

Embodiment 2

[0028] Add 2-(3-hydroxyl-1-adamantane)-2-oxoacetic acid (20.0g, 89mmol) and quinoline alkaloid cinchonine sulfonate (0.8g ), 5% aqueous sodium hydroxide solution 80g and p-hydroxybenzylamine (15.4g, 0.125mol), the mixture was heated up to 40°C, concentrated after 12 hours of reaction, reacted with concentrated hydrochloric acid to adjust the pH value of the reaction solution to about 6 and then frozen to - The product was precipitated at about 5°C, and 19.4 g of the product was obtained by freeze-drying after suction filtration, with an ee value of 98.5% and a yield of 96.8%.

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 relates to a (s)-3-hydroxyadamantylglycine preparation method, which takes 2-(3-hydroxy-1-adamantane)-2-glyoxalic acid as a raw material, in a sodium hydroxide aqueous solution, under effects of a chiral catalyst and p-hydroxybenzylamine, (s)-3-hydroxyadamantylglycine can be generated, wherein the chiral catalyst is a quinoline alkaloid cinchonine derivative. The preparation method has the characteristics of mild reaction condition, high product yield, high purity and high enantiomer selectivity, has the advantages of short route, simple operation, no pollution and easy industrial production, and is the economic and simple method.

Description

technical field [0001] The invention relates to a preparation method of (s)-3-hydroxyadamantane glycine, which belongs to the field of chemical synthesis. Background technique [0002] (s)-3-Hydroxyadamantane glycine is a kind of important pharmaceutical intermediate, is the important raw material of synthetic treatment diabetes chiral drug saxagliptin (trade name Onglyza), and the chemical formula of saxagliptin is (1S, 3S, 5S)-2-[(2S)-2-amino-2-(3-hydroxytricyclo[3.3.1.1]dec-1-yl)acetyl]-2-nitrobicyclo[3.1.0]hexyl Alkane-3-carbonitrile monohydrochloride. This product is marketed by Bristol-Myers Squibb. The important advantages of the drug are that it is convenient to use, has few adverse reactions, has a low risk of hypoglycemia and does not cause weight gain, and has a good market prospect. [0003] The reported synthetic routes mainly use PDH (phenylalanine dehydrogenase) / FDH (formate dehydrogenase) enzymes to catalyze the reductive amination of 2-(3-hydroxy-1-adaman...

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 Patents(China)
IPC IPC(8): C07C229/28C07C227/32C07C227/08
Inventor 宗乾收汪剑波宋熙熙邱观音生包琳缪程平张洋
Owner JIAXING UNIV
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