Synthetic method of benzopyran chiral compound

A technology of chiral compounds and benzopyrans, applied in the field of chemistry, can solve the problems of high price, low yield, unfavorable for large-scale application, etc., and achieves easy availability of raw materials, high optical purity, and is conducive to large-scale applications. Effects of production applications

Active Publication Date: 2013-04-03
GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Using chiral amines to induce crystallization, the yield is generally low, and the chiral resolving agent is expensive
However, the use of chiral columns for separation is very expensive, which is not conducive to large-scale applications

Method used

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  • Synthetic method of benzopyran chiral compound
  • Synthetic method of benzopyran chiral compound
  • Synthetic method of benzopyran chiral compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Synthesis of (S)-7-tert-butyl-6-chloro-2-trifluoromethyl-2H-chromene-3-carboxylic acid

[0046] The synthetic route of (S)-7-tert-butyl-6-chloro-2-trifluoromethyl-2H-chromene-3-carboxylic acid is as follows:

[0047]

[0048] Specific steps are as follows:

[0049] Step 1: Synthesis of (S)-7-tert-butyl-6-chloro-2-trifluoromethyl-2H-benzopyran-3-aldehyde

[0050] The compound 4-tert-butyl-5-chloro-2-hydroxybenzaldehyde (1.0g, 4.7mmol) with the structure of formula I, the compound 4,4,4-trifluorobut-2-enal with the structure of formula II (1.16g, 9.4mmol), chiral catalyst (2S)-2-[diphenyl[(trimethylsilyl)oxy]methyl]-pyrrolidine (0.31g, 0.94mmol), chemical additives Nitrobenzoic acid (0.16 g, 0.94 mmol) was mixed in 50 mL of ethyl acetate. The reaction solution was stirred at 25°C for 24 hours. After the reaction was completed, the product (S)-7-tert-butyl-6-chloro-2-trifluoromethyl-2H-benzopyran-3-aldehyde was obtained by column chromatography (structure as follows...

Embodiment 2

[0063] Synthesis of (S)-6-chloro-5,7-deuterodimethyl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid

[0064] The synthetic route of (S)-6-chloro-5,7-deuterodimethyl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid is as follows:

[0065]

[0066] Specific steps are as follows:

[0067] Step 1: Synthesis of (S)-6-chloro-5,7-deuterodimethyl-2-(trifluoromethyl)-2H-benzopyran-3-aldehyde

[0068] The compound 3-chloro-6-hydroxyl-2,4-deuterated dimethylbenzaldehyde (1.0g, 5.2mmol) with the structure of formula I, the compound 4,4,4-trifluorobutanol with the structure of formula II 2-enal (1.3g, 10.4mmol), chiral catalyst (2S)-2-[diphenyl[(trimethylsilyl)oxy]methyl]-pyrrolidine (0.34g, 1.04mmol), Chemical Additions p-Nitrobenzoic acid (0.34 g, 2.08 mmol) was mixed in 50 mL of chloroform. The reaction solution was stirred at 25°C for 48 hours. After the reaction, the product (S)-6-chloro-5,7-deuterodimethyl-2-(trifluoromethyl)-2H-benzo Pyran-3-aldehyde (structure as follows...

Embodiment 3

[0082] Synthesis of (S)-6-bromo-5,7-deuterodimethyl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid

[0083] The synthetic route of (S)-6-bromo-5,7-deuterodimethyl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid is as follows:

[0084]

[0085] Specific steps are as follows:

[0086] Step 1: Synthesis of (S)-6-bromo-5,7-deuterodimethyl-2-(trifluoromethyl)-2H-benzopyran-3-aldehyde

[0087] The compound 3-bromo-6-hydroxyl-2,4-deuterodimethylbenzaldehyde (1.0g, 4.3mmol) with the structure of formula I, the compound 4,4,4-trifluorobutanol with the structure of formula II 2-enal (1.1g, 8.6mmol), chiral catalyst (2S)-2-[diphenyl[(trimethylsilyl)oxy]methyl]-pyrrolidine (0.28g, 0.86mmol), The chemical additive o-nitrobenzoic acid (0.14g, 0.86mmol) was mixed in 50mL chloroform. The reaction solution was stirred at 25°C for 24 hours. After the reaction, the product (S)-6-bromo-5,7 -Deuterated dimethyl-2-(trifluoromethyl)-2H-benzopyran-3-al (structure as follows) 1.2g (yield: 8...

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Abstract

The invention discloses a synthetic method of a benzopyran chiral compound. The method comprises the following steps: a compound with the structural formula I and a compound with the structural formula II carry out the condensation reaction to generate a compound with the structural formula III, and the compound with the structural formula III is oxidized to obtain the benzopyran chiral compound; the chemical additive adopts a benzoic acid or a substituted benzoic acid compound; and the chiral catalyst is a diphenyl prolinol ester compound or dinaphthyl prolinol ester compound. The synthetic method has the advantages that under the mild condition, relatively cheap raw materials are used, the benzopyran chiral compound derivate is synthesized with high yield, and the derivate is high in optical purity, accessible in raw material, and beneficial for large-scale production and application.

Description

technical field [0001] The invention belongs to the field of chemistry, and in particular relates to a synthesis method of benzopyran chiral compounds and derivatives thereof. Background technique [0002] Chirality is the basic characteristic of life process, and most of the organic molecules that make up living organisms are chiral molecules. Most of the drugs used by people have chirality, which are called chiral drugs, and these chiral drugs have two enantiomers. Enantiomers are a lot like your left and right hands, they look very similar, but not identical. When a chiral drug enters a living body, its two enantiomers usually exhibit different biological activities. With chiral drugs, one isomer may be effective, while the other may be ineffective or even harmful. Chiral pharmacy uses this principle of compounds to develop drugs with high efficacy and few side effects. In terms of clinical treatment, taking enantiomerically pure chiral drugs can not only eliminate th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D311/58
Inventor 张艳梅约翰·泰勒王贻灿刘健齐
Owner GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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