Synthesis method of trifluoromethylated 1, 3-oxazine compound

A technology of trifluoromethylation and synthesis method, which is applied in the field of synthesis of trifluoromethylated 1,3-oxazine compounds, and can solve the problems of poor reaction atom economy and limited industrial application

Active Publication Date: 2020-09-25
ZUNYI MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the existing synthetic method of this type of compound, use more expensive 3,3-dimethyl-1-(trifluoromethyl)-1,2-benzoiodooxolane) as trifluoromethyl source ( Org Lett 2019,21,4657), the poor atom economy of the reaction limits the industrial application of this class of molecules

Method used

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  • Synthesis method of trifluoromethylated 1, 3-oxazine compound
  • Synthesis method of trifluoromethylated 1, 3-oxazine compound
  • Synthesis method of trifluoromethylated 1, 3-oxazine compound

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Experimental program
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Embodiment 1

[0023] A method for synthesizing trifluoromethylated 1,3-oxazine compounds, comprising the following steps: 1) Using p-toluimide homoallyl ester as a substrate, sodium trifluoromethanesulfinate Is a trifluoromethyl reagent, copper acetate is a copper salt, silver acetate is a silver salt, and acetonitrile is a reaction solvent;

[0024] 2) Combine p-methylbenzimide homoallyl ester (37.8mg, 0.2mmol), sodium trifluoromethanesulfinate (62.4mg, 0.4mmol), silver acetate (66.8mg, 0.4mmol), acetic acid Copper (7.2mg, 0.04mmol) was sequentially added to stirring acetonitrile (2mL), and reacted at 80°C for 24 hours. After extraction, drying, concentration and silica gel column chromatography, a colorless liquid (18.2mg, 71%) was obtained. , The chemical reaction formula 1 is:

[0025]

[0026] The product testing data is as follows:

[0027] 1 H NMR(400MHz, CDCl 3 )δ7.78(d,J=8.3Hz,2H), 7.16(d,J=8.0Hz,2H), 4.49–4.36(m,1H), 4.34–4.21(m,1H), 3.92–3.81(m ,1H), 2.76–2.65(m,1H), 2.38(s,3H), 2.25...

Embodiment 2

[0029] A method for synthesizing trifluoromethylated 1,3-oxazine compounds, comprising the following steps: 1) Using p-toluimide homoallyl ester as the substrate, silver benzoate as the carboxyl reagent, and acetic acid Copper is a copper salt, and acetonitrile is a reaction solvent;

[0030] 2) Combine p-methylbenzimide homoallyl ester (44.5mg, 0.2mmol), sodium trifluoromethanesulfinate (62.4mg, 0.4mmol), silver acetate (66.8mg, 0.4mmol), acetic acid Copper (7.2mg, 0.04mmol) was sequentially added to stirring acetonitrile (2mL), reacted at 80°C for 24 hours, and then extracted, dried, concentrated and silica gel column chromatography was used to obtain a colorless liquid (37.5mg, 64%) , The chemical reaction formula 2 is:

[0031]

[0032] The product testing data is as follows:

[0033] 1 H NMR(400MHz, CDCl 3 )δ8.40(s,1H), 8.04(d,J=8.6Hz,1H),7.93-7.89(m,1H),7.85(t,J=7.1Hz,2H),7.57-7.44(m,2H ), 4.56–4.43(m,1H), 4.41–4.34(m,1H), 4.03–3.92(m,1H), 2.89–2.66(m,1H), 2.37–2.24(m,2H), 1...

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Abstract

The invention relates to a synthetic method of a trifluoromethylated 1, 3-oxazine compound, which comprises the following steps: 1) selecting aryl formamide homoallyl ester, sodium trifluoromethanesulfinate, silver salt and copper salt, and sequentially adding into an organic solvent; and 2) heating to a proper temperature to prepare the trifluoromethyl substituted 1, 3-oxazine compound. Accordingto the method, aryl formamide homoallyl ester is used as a substrate, cheap sodium trifluoromethanesulfinate is used as a trifluoromethyl reagent, the trifluoromethyl substituted 1, 3-oxazine compound is synthesized under the action of copper salt and silver salt, and an economic synthesis route is provided for the compound.

Description

Technical field [0001] The invention relates to a method for synthesizing trifluoromethylated 1,3-oxazine compounds and belongs to the technical field of organic synthesis. Background technique [0002] Trifluoromethyl is a special type of fluorine-containing group. The structure contains three fluorocarbon (C-F) bonds, giving it many fluorine-containing properties. Utilizing the special properties of trifluoromethyl, the introduction of trifluoromethyl into active drug molecules can significantly enhance the metabolism of the parent drug molecule by changing the dipole moment, acidity, lipophilicity, polarity and chemical stability of the parent molecule Stability and fat solubility, and can affect the absorption and distribution of the drug in the body and the interaction with the target. For example, after changing the C12 and C13 methyl groups of the tumor inhibitor epothilone D, which has a good market prospect, to trifluoromethyl, the stability of the drug molecule is enha...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D265/08
CPCC07D265/08
Inventor 牟学清陈永正单静
Owner ZUNYI MEDICAL UNIVERSITY
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