A kind of chiral 3-(2-nitroethyl)tetrahydrofuran compound and its preparation method

A technology of hydroxytetrahydrofuran and nitroethyl is applied in the field of chiral 3-(2-nitroethyl)tetrahydrofuran compound and its preparation, and in the field of tetrahydrofuran compound material, which can solve the problem that the synthesis method of 3-substituted tetrahydrofuran compound is rare, and the hand is limited. The application of 3-substituted tetrahydrofuran compounds is difficult to meet the requirements of practical application, and the effect of good application prospect, novel structure and short reaction time is achieved.

Active Publication Date: 2016-01-20
杭州三隆新材料有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In the prior art, there are many reports on the synthesis of 2-substituted, 2,3-disubstituted, 2,5-disubstituted, trisubstituted, and tetrasubstituted tetrahydrofuran compounds, and because the 3-substituted position of tetrahydrofuran is difficult to be activated by catalysts, Therefore, reports on the synthesis method of 3-substituted tetrahydrofuran compounds are relatively rare, especially on the synthesis of chiral 3-substituted tetrahydrofuran compounds.
[0004] In 2013, MasafumiHirano et al. reported the ene dimerization reaction of 3,4-dihydrofuran and acrylate under the catalysis of chiral ruthenium to obtain chiral 3-substituted tetrahydrofuran products; but the reaction time was as long as seven days, and the product The ee value (enantiomeric excess value) is low, only 80%, and it is difficult to meet the requirements of practical applications (see: YukiHiroi, NobuyukiKomine, SanshiroKomiya, and MasafumiHirano. Org. Lett. 2013, 15 ,2486-2489)
Due to the lack of effective synthetic methods, the application of chiral 3-substituted tetrahydrofuran compounds in drug synthesis is limited

Method used

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  • A kind of chiral 3-(2-nitroethyl)tetrahydrofuran compound and its preparation method
  • A kind of chiral 3-(2-nitroethyl)tetrahydrofuran compound and its preparation method
  • A kind of chiral 3-(2-nitroethyl)tetrahydrofuran compound and its preparation method

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Experimental program
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Effect test

Embodiment 1

[0037] Put 1mmol of 1-nitro, 2-(3-nitrophenyl)-ethene, 2.5mmol of 2-hydroxytetrahydrofuran and 0.4mmol of catalyst (R 2 = phenyl, R 3 = trimethylsilyl group) was dissolved in 3 mL of chloroform, 1 mmol of acetic acid was added, and the reaction was carried out at 25 °C for 12 hours until the reaction of nitrostyrene was complete. The reaction solution was washed with 5 ml of 1 mol / L hydrochloric acid, then extracted with dichloromethane, the combined organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. Add 12mL of dichloromethane to the residue, then add 3mmol of triethylsilane, slowly add 3mmol of boron trifluoride ether under stirring at room temperature, and react at room temperature for 2 hours; then the solvent is removed by rotary evaporation, and the residue is subjected to silica gel column chromatography. Ether: ethyl acetate = 2:1 elution, the light yellow solid is obtained as the pr...

Embodiment 2

[0042] Put 1mmol of 1-nitro, 2-(3-nitrophenyl)-ethene, 2.5mmol of 2-hydroxytetrahydrofuran and 0.4mmol of catalyst (R 2 =3,5-ditrifluoromethylphenyl, R 3 = trimethylsilyl) was dissolved in 3mL toluene, 0.4mmol acetic acid was added, and the reaction was carried out at 25°C for 15 hours until the nitrostyrene reaction was complete. The reaction solution was washed with 5 ml of 1 mol / L hydrochloric acid, then extracted with dichloromethane, the combined organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. Add 12mL of dichloromethane to the residue, then add 3mmol of triethylsilane, slowly add 3mmol of boron trifluoride diethyl ether under stirring at room temperature, and react at room temperature for 2 hours; then the solvent is removed by rotary evaporation, and the residue is subjected to silica gel column chromatography. Ether: ethyl acetate = 2:1 elution, 170 mg of light yellow solid produc...

Embodiment 3

[0044] Put 1mmol of 1-nitro, 2-(3-nitrophenyl)-ethene, 2.5mmol of 2-hydroxytetrahydrofuran and 0.4mmol of catalyst (R 2 = phenyl, R 3 = tert-butyldimethylsilyl) was dissolved in 3 mL of N,N-dimethylformamide, 0.4 mmol acetic acid was added, and the reaction was carried out at 25 °C for 12 hours until the nitrostyrene reaction was complete. The reaction solution was washed with 5 ml of 1 mol / L hydrochloric acid, then extracted with dichloromethane, the combined organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. Add 12mL of dichloromethane to the residue, then add 3mmol of triethylsilane, slowly add 3mmol of boron trifluoride diethyl ether under stirring at room temperature, and react at room temperature for 2 hours; then the solvent is removed by rotary evaporation, and the residue is subjected to silica gel column chromatography. Ether: ethyl acetate = 2:1 eluted to obtain 181 mg of light ye...

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Abstract

The invention discloses a chiral 3-(2-nitro ethyl) tetrahydrofuran compound and a preparation method thereof. The preparation method specifically comprises the following steps: performing Michael addition reaction on 2-hydroxytetrahydrofuran and nitroalkene by using proline-derived chiral pyrrolidine serving as a catalyst, and performing Et3SiH / BF3.Et2O reduction to remove 2-hydroxyl to obtain the product. According to the chiral 3-(2-nitro ethyl) tetrahydrofuran compound and the preparation method for the same, the compound is novel in structure and high in enantiomeric purity; a plurality of active natural products and medicaments contain tetrahydrofuran structures, so that the compound has high application value in the total synthesis of the natural products and the discovery of new medicaments, and has good application prospect.

Description

technical field [0001] The invention relates to a tetrahydrofuran compound material, in particular to a chiral 3-(2-nitroethyl) tetrahydrofuran compound and a preparation method thereof, belonging to the field of organic synthesis. Background technique [0002] Tetrahydrofuran compounds are a class of important skeleton structures with special medicinal compounds. They are widely found in many natural products and drugs. The most common one is the deoxyribonucleic acid unit in the DNA structure. In addition, many natural products such as five-carbon sugars, Polyether natural products and some lignins contain one or more tetrahydrofuran rings. Clinically used drugs such as antiviral and anticancer nucleoside drugs and antibacterial posaconazole all contain tetrahydrofuran structures. The antiviral drug Amp Navir contains a chiral 3-oxotetrahydrofuran moiety. [0003] In the prior art, there are many reports on the synthesis of 2-substituted, 2,3-disubstituted, 2,5-disubstitu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D307/10C07D307/12C07D307/38
CPCC07D307/10C07D307/12C07D307/38
Inventor 张士磊邱刚胡延维陈韶华苑来旗刘石惠王建强朱亚东
Owner 杭州三隆新材料有限公司
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