Synthesizing method, partial intermediate products and final products of chiral beta-alkamine derivative

A technology of amino alcohols and synthesis methods, which is applied in the field of synthesis of chiral β-amino alcohol derivatives, and can solve problems such as difficult control of reaction conditions, difficulty in obtaining raw materials, and unsuitability for large-scale production.

Active Publication Date: 2010-06-02
ASYMCHEM LIFE SCI TIANJIN
View PDF0 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The synthetic method that has been reported above is because the reaction condition is difficult to control, thus the obtained product is easy to racemize or the purity (ee) value of enantiomer is not high, or raw material is not easy to obtain etc., is not suitable for large-scale production

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
  • Synthesizing method, partial intermediate products and final products of chiral beta-alkamine derivative
  • Synthesizing method, partial intermediate products and final products of chiral beta-alkamine derivative
  • Synthesizing method, partial intermediate products and final products of chiral beta-alkamine derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] (1) Preparation of R-1-(3-bromophenylamino)-3-chloro-propane-2-ol,

[0033] Add 100g (R) epichlorohydrin (1eq) and 204.6g meta-bromoaniline (1.1eq) into a 1L four-neck flask, and add 12.1g of stannous chloride dihydrate (SnCl) to the system in two batches 2 .2H 2 O) (0.05eq), the addition is complete, stirring at 25±1℃, GC tracking until the reaction is over, 400mL water is added to terminate the reaction, the system is extracted with 600mL methyl tert-butyl ether, the organic phase is then washed with 150mL saturated brine, and reduced Dry organic phase, obtain product 185.9g, yield 65%, enantiomeric purity (ee): 99.8%, gas phase purity (GC): 94%.

[0034] H-NMR: (300MHz, DMSO-d 6 ), δ 2.991-3.058 (dd, CH2NH, 1H), δ 3.138-3.198 (dd, CH2NH, 1H), δ 3.553-3.608 (dd, CH2Cl, 1H), δ 3.648-3.699 (dd, CH2Cl , 1H), δ 3.800-3.836 (m, CH, 1H), δ 5.390 (b, NH, 1H), δ 5.971 (b, OH, 1H), δ 6.587 (d, Ph-H, 1H) ), δ 6.615 (d, Ph-H, 1H), δ 6.772 (s, Ph-H, 1H), δ 6.995 (t, Ph-H, 1H).

[003...

Embodiment 2

[0042] (1) Preparation of R-1-(4-fluorophenylamino)-3-chloro-propane-2-ol,

[0043] Add 150g (R) epichlorohydrin (1eq) and 189g p-fluoroaniline (1.05eq) into a 1L four-neck flask, and add 21.9g stannous chloride dihydrate (SnCl) to the system in four batches 2 .2H 2 O) (0.06eq), the addition is complete, stirring at 26±1℃, GC tracking to the end of the reaction, 400mL of water is added to terminate the reaction, the system is extracted with 800mL of methyl tert-butyl ether, the organic phase is washed with 200mL of saturated brine, and reduced Dry organic phase to obtain crude product 358g, methyl tert-butyl ether: petroleum ether = 1:3 recrystallized to obtain product 210g, yield 63.6%, enantiomeric purity (ee): 99.6%, gas phase purity (GC): 96%.

[0044] H-NMR: (300MHz, DMSO-d 6 ), δ3.032-3.075(dd, CH2NH, 1H), δ3.158-3.218(dd, CH2NH, 1H), δ3.576-3.630(dd, CH2Cl, 1H), δ3.670-3.719(dd, CH2Cl , 1H), δ 3.810-3.846 (m, CH, 1H), δ 5.503 (b, NH, 1H), δ 5.998 (b, OH, 1H), δ 6.501 (m, P...

Embodiment 3

[0053] (1) Preparation of R-1-(4-bromophenylamino)-3-chloro-propane-2-ol,

[0054] Add 50g (R) epichlorohydrin and 106.9g 4-bromoaniline (1.15eq) into a 500mL four-neck flask, add 7.05g lithium bromide (0.15eq) into the system in two batches, after the addition is complete, stir at 27±1℃, GC tracked to the end of the reaction, added 300 mL of water to terminate the reaction, the system was extracted with 600 mL of methyl tert-butyl ether, the organic phase was washed with 150 mL of saturated brine, and the organic phase was shrunk to obtain 71 g of product, with a yield of 50%, enantiomer Purity (ee): 99.7%, gas phase purity (GC): 95%.

[0055] H-NMR: (300MHz, DMSO-d 6 ), δ 2.701-3.078 (dd, CH2NH, 1H), δ 3.158-3.218 (dd, CH2NH, 1H), δ 3.532-3.587 (dd, CH2Cl, 1H), δ 3.627-3.678 (dd, CH2Cl , 1H), δ 3.806-3.847 (m, CH, 1H), δ 5.270 (b, NH, 1H), δ 5.983 (b, OH, 1H), δ 6.560 (d, Ph-H, 1H) ), δ 6.651 (d, Ph-H, 1H), δ 6.790 (d, Ph-H, 1H), δ 6.974 (d, Ph-H, 1H).

[0056] (2) Preparation ...

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 synthesizing method, partial intermediate products and final products of a chiral beta-alkamine derivative. The synthesizing method of the chiral beta-alkamine derivative is characterized by comprising the steps of: selecting commercialized materials in the market and NH2R2 as initial materials, wherein R2 is a Cl-C6 alkyl group, a C3-C6 naphthenic base and an aryl group or an aryloxy; obtaining the intermediate products and the final products through a chemical reaction process with moderate conditions, wherein R1 and R2 are the Cl-C6 alkyl group, the C3-C6 naphthenic base and the aryl group or the aryloxy, and a chiral center is in an S or R shape. The invention has the advantages that the adopted materials are easy to obtain and at low price and can meet the requirements of large-scale production, chiral compounds are used as the initial materials, optical purity is retained in consequent reaction without finding racemization, and committed steps accord with the requirements of the current green chemistry; in addition, the invention has the advantages of simple synthesizing method, good selectivity, high yield coefficient, easy operation and good market benefits.

Description

(1) Technical field: [0001] The present invention relates to a method for synthesizing chiral β-amino alcohol derivatives and part of intermediate products and final products, especially The synthetic method and some of its intermediate and final products. (2) Background technology: [0002] The β-amino alcohol structure is the main pharmacodynamic group of many drugs. Chiral β-amino alcohols have important uses in organic synthesis. They are ideal chiral building blocks and excellent organic catalysts. They are still asymmetric Chiral ligands are very important in catalytic reactions, which can coordinate with transition metal ions to form chiral catalysts, catalyze asymmetric hydrogenation and asymmetric hydrogen transfer reactions, etc. In addition, recent studies have found chiral β-amino alcohols The compounds of the structure are used in the synthesis of heterocyclic compounds. These compounds help prevent the absorption of cholesterol and have good biological activity in ...

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): C07C213/00C07C213/04C07C215/16C07D303/36C07C217/64
Inventor 洪浩马特·约翰森李康应
Owner ASYMCHEM LIFE SCI TIANJIN
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