Method for synthesizing optically active benzo carboxylic acid ester compound through asymmetric addition reaction

An ester compound, addition reaction technology, applied in organic chemistry methods, organic chemistry and other directions, can solve problems to be explored, and achieve the effects of good enantioselectivity, simple post-processing and mild reaction conditions

Active Publication Date: 2021-08-03
HENAN NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] So far, the formation of carbon-carbon bonds at the carbon-2 position of azlactone has been successful

Method used

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  • Method for synthesizing optically active benzo carboxylic acid ester compound through asymmetric addition reaction
  • Method for synthesizing optically active benzo carboxylic acid ester compound through asymmetric addition reaction
  • Method for synthesizing optically active benzo carboxylic acid ester compound through asymmetric addition reaction

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022]

[0023]

[0024] a tert-leucine 1, trifluoroacetic anhydride, dicyclohexylcarbodiimide, and 1.0 mL of anhydrous solvent were stirred well at room temperature for several hours. Then the catalyst (0.01 mmol, 10 mol%) and azocarboxylate 2a (0.10 mmol) were slowly added to the reaction system and stirred for 12 hours. b The reaction time of the first step. c Isolated yield. d The ee value is obtained by chiral column HPLC chiral analysis.

[0025] In the screening process of the reaction conditions, the influence of different catalysts on the reaction (entries 1-6) was first investigated, and finally the catalyst C3 was determined to be the best catalyst, and then the equivalent ratio of dicyclohexylcarbodiimide was investigated. Influence (entries 6-9), finally determined that the equivalent of dicyclohexylcarbodiimide is 8 times equivalent. Subsequently, the influence of the equivalent ratio of tert-leucine on the reaction was examined (entries 9-10), and it w...

Embodiment 2

[0029]

[0030] At room temperature, 1 mL of mesitylene was added to a 10 mL round-bottomed flask after anhydrous treatment, and tert-leucine 1 (26.2 mg, 0.20 mmol, 2 eq), trifluoroacetic anhydride (50.4 mg, 0.24 mmol, 2.4 eq ) and dicyclohexylcarbodiimide (165.0mg, 0.8mmol, 8eq) were added sequentially and stirred for 8 hours, then azocarboxylate 2b (23.1mg, 0.10mmol) and catalyst C3 (4.4mg) were added slowly In the solvent, stir at 25°C for 12h. TLC spot plate tracked until raw material 2b disappeared, filtered to remove insoluble matter, filter residue was washed with dichloromethane, and directly flash silica gel column chromatography (eluent sherwood oil / ethyl acetate=1 / 10-1 / 5 after decompression solvent removal) ) separation and purification to obtain light yellow oily product 6b, the yield is 82%; HPLC (CHIRALPAK IF, n-hexane / isopropanol=90 / 10, flow rate 1.0mL / min, λ=220nm)t R (1)=6.297min,t R (2)=6.803min, 89%ee; (c 1.0, CHCl 3 ); 1 H NMR (600MHz, CDCl 3 )δ7....

Embodiment 3

[0032]

[0033] At room temperature, 1 mL of mesitylene was added to a 10 mL round-bottomed flask after anhydrous treatment, and tert-leucine 1 (26.2 mg, 0.20 mmol, 2 eq), trifluoroacetic anhydride (50.4 mg, 0.24 mmol, 2.4 eq ) and dicyclohexylcarbodiimide (165.0mg, 0.8mmol, 8eq) were added sequentially and stirred for 8 hours, then azocarboxylate 2c (22.4mg, 0.10mmol) and catalyst C3 (4.4mg) were added slowly In the solvent, stir at 25°C for 12h. TLC point plate tracked until the raw material 2c disappeared, filtered to remove insoluble matter, and the filter residue was washed with dichloromethane. After removing the solvent under reduced pressure, direct flash silica gel column chromatography (eluent was petroleum ether / ethyl acetate=1 / 10-1 / 5) Separation and purification to obtain colorless oily product 3c with a yield of 86%; HPLC (NuAnalytical-FLMNZ 2 , n-hexane / isopropanol=94 / 6, flow rate 1.0mL / min, λ=220nm)t R (1) = 6.447min, t R (2)=7.957min, 92%ee; (c 1.0, CH...

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Abstract

The invention discloses a method for synthesizing an optically active benzo carboxylic acid ester compound through an asymmetric addition reaction, and belongs to the technical field of asymmetric synthesis in organic chemistry. Tert-leucine is used as an initial raw material and reacts with trifluoroacetic anhydride to generate a 2-trifluoroalkyl oxazole-5 (2H) ketone intermediate product, and then in the presence of a chiral bifunctional tertiary amine urea catalyst, the optical benzo carboxylic acid ester compound is synthesized through asymmetric addition reaction and one-pot two-step synthesis. The method has the advantages that the reaction raw materials are easy to obtain, the catalyst is simple in structure, the catalytic efficiency is high, the reaction conditions are mild, post-treatment is simple, and the high-optical-activity benzo carboxylic acid ester compound is obtained.

Description

technical field [0001] The invention belongs to the technical field of asymmetric synthesis in organic chemistry, and in particular relates to a method for synthesizing optically active benzocarboxylate compounds through asymmetric addition reaction. Background technique [0002] As an important method for the synthesis of optically active benzocarboxylate compounds, based on the selectivity of the 4-position of azlactone carbon and the selectivity of the 2-position of carbon to generate tertiary carbon or nitroxide amino derivatives with quaternary carbon chiral centers, in Extensive research has been carried out over the past few decades. The introduction of perfluoroalkyl functional groups in the parent molecule will significantly affect its chemical, physical and biological properties, and many known chiral molecules containing trifluoromethyl groups have important practical value. [0003] So far, the formation of carbon-carbon bonds at the carbon-2 position of azlacto...

Claims

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Application Information

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IPC IPC(8): C07D263/48
CPCC07D263/48C07B2200/07
Inventor 朱博范慧慧常俊标
Owner HENAN NORMAL UNIV
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