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A kind of synthetic method of chiral α-aryl propionate compound

A technology of aryl propionate and synthesis method, applied in the preparation of organic compounds, chemical instruments and methods, preparation of carboxylate, etc., can solve the problems of numerous reaction steps, difficult preparation and storage of reaction raw materials, harsh reaction temperature and the like , to achieve the effect of low price, good substrate adaptability and safe reaction

Inactive Publication Date: 2019-05-28
SHANGHAI INST OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] In order to solve the problems in the current synthesis method of α-aryl propionate compounds such as difficult preparation and storage of reaction raw materials, harsh reaction temperature, and various reaction steps, the purpose of the present invention is to provide a chiral α- -The synthetic method of aryl propionate compound

Method used

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  • A kind of synthetic method of chiral α-aryl propionate compound
  • A kind of synthetic method of chiral α-aryl propionate compound
  • A kind of synthetic method of chiral α-aryl propionate compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Taking methyl p-bromobenzoate and ethyl 2-chloropropionate as raw materials to synthesize product 1, its structural formula is:

[0031]

[0032] To a dry Schlenk tube were added methyl p-bromobenzoate (0.225 mmol, 0.0484 g), the ligand 4,4'-diisopropyl-4,4',5,5'-tetrahydro-2,2 '-isoxazole (0.0225mmol, 0.0050g), zinc powder (0.3mmol, 0.0200g), anhydrous magnesium chloride (0.075mmol, 0.0071g), anhydrous lithium chloride (0.075mmol, 0.0060g), and then Schlenk The tube was moved into the glove box, and NiCl was added 2 dme (0.015mmol, 0.0033g), tetrabutylammonium bromide (0.03mmol, 0.0097g) and then the Schlenk tube was removed from the glove box, and ethyl 2-chloropropionate (0.15mmol, 0.0205g) was added with a micro syringe, Finally, THF 1ml was added with a syringe, and stirred in an ice-water bath to room temperature slowly for 8-12h. After the reaction, without post-treatment, the transparent oil 1 was directly separated by column chromatography (ethyl acetate:p...

Embodiment 2

[0036] Taking p-cyanobromobenzene and ethyl 2-chloropropionate as raw materials to synthesize product 2, its structural formula is:

[0037]

[0038] Add p-cyanobromobenzene (0.225 mmol, 0.0400 g), ligand 4,4'-diisopropyl-4,4', 5,5'-tetrahydro-2,2' sequentially to a dry Schlenk tube -isoxazole (0.0225mmol, 0.0050g,), zinc powder (0.3mmol, 0.0200g), anhydrous magnesium chloride (0.075mmol, 0.0071g,), anhydrous lithium chloride (0.075mmol, 0.0060g), and then The Schlenk tube was moved into the glove box and NiCl was added 2 dme (0.015mmol, 0.0033g), tetrabutylammonium bromide (0.03mmol, 0.0097g) and then the Schlenk tube was removed from the glove box, and ethyl 2-chloropropionate (0.15mmol, 0.0205g) was added with a micro syringe, Finally, THF 1ml was added with a syringe, and stirred in an ice-water bath to room temperature slowly for 8-12h. After the reaction, without post-treatment, the transparent oil 2 was directly separated by column chromatography (ethyl acetate:pet...

Embodiment 3

[0041] Using methyl 2-bromobenzoate and ethyl 2-chloropropionate as raw materials to synthesize product 3, its structural formula is:

[0042]

[0043] To a dry Schlenk tube were sequentially added methyl 2-bromobenzoate (0.225 mmol, 0.0484 g), the ligand 4,4'-diisopropyl-4,4',5,5'-tetrahydro-2, 2'-isoxazole (0.0225mmol, 0.0050g), zinc powder (0.3mmol, 0.0200g), anhydrous magnesium chloride (0.075mmol, 0.0071g,), anhydrous lithium chloride (0.075mmol, 0.0060g), and Move the Schlenk tube into the glove box and add NiCl 2dme (0.015mmol, 0.0033g), tetrabutylammonium bromide (0.03mmol, 0.0097g) and then the Schlenk tube was removed from the glove box, and ethyl 2-chloropropionate (0.15mmol, 0.0205g) was added with a micro syringe, Finally, THF 1ml was added with a syringe, and stirred in an ice-water bath to room temperature slowly for 8-12h. After the reaction, without post-treatment, the transparent oily substance 3 can be obtained directly by column chromatography (ethyl a...

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Abstract

The invention discloses a synthesis method of a chiral alpha-arylpropionate compound. The chiral alpha-arylpropionate compound is prepared by reacting 2-halopropionate and aryl halide used as raw materials under the action of a chiral ligand and a catalyst with zinc powder as a reducing agent and anhydrous magnesium bromide, anhydrous lithium chloride and tetrabutylammonium bromide as additives, wherein the catalyst is nickel chloride dimethoxyethane NiCl2.dme. The raw materials are cheap and available, no organic metal reagent is required to be prepared, the reaction condition is mild, and the method is convenient to operate and has high significance and value.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a synthesis method of chiral α-aryl propionate compounds. technical background [0002] Chiral α-aryl propionate compounds are very important prodrugs (NSAIDS) and intermediates in organic synthesis. Non-steroidal anti-inflammatory drugs (NSAIDS) are one of the most used drugs in the world. About 30 million people use it every day around the world. With the increase in the use of NSAIDs, the market demand for this type of drug is also increasing, and the quality is also required to be continuously improved, which greatly promotes the development of its synthesis process. [0003] In 2005, Gregory C.Fu disclosed a method (J.Am.Chem.Soc. 2005, 127, 4594–4595). [0004] In 2014, Patrick J.Walsh et al. used cobalt iodide as a catalyst, chiral ligands in tetrahydrofuran, and 2-bromine-substituted esters and aromatic Grignard reagents as raw materials to asymm...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C67/343C07C69/76C07C69/65C07C69/616C07C253/30C07C255/57
CPCC07C67/343C07C253/30C07C69/76C07C69/65C07C69/616C07C255/57
Inventor 张兴华刘建东龚和贵陈海峰
Owner SHANGHAI INST OF TECH