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Synthesis method of spiro-oxindole gamma-butyrolactone compound

A technology of spiro-epoxidized indole and synthesis method, applied in the direction of organic chemistry and the like, can solve the problems of less synthesis and research

Inactive Publication Date: 2017-05-31
CHINA PHARM UNIV
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Problems solved by technology

[0005] Spiroepoxindole γ-butyrolactones are an important subtype of spiroepoxindole derivatives, but their synthesis and research are less

Method used

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  • Synthesis method of spiro-oxindole gamma-butyrolactone compound
  • Synthesis method of spiro-oxindole gamma-butyrolactone compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Example 1: Reaction of 2-(1-benzyl-2-oxoindol-3-yl)acetic acid and trifluoroacetophenone

[0019] 56.2 mg (0.2 mmol) of 2-(1-benzyl-2-oxoindol-3-yl) acetic acid, 52.2 mg (0.3 mmol) of trifluoroacetophenone, N, N'- Carbonyldiimidazole 39mg (0.24mmol), cesium carbonate 130mg (0.4mmol), p-toluenesulfonic acid 34.4mg (0.2mmol) and dichloromethane 2mL were placed in a 25mL two-necked bottle, and reacted at 25°C for 4h. Concentrate, elute through column chromatography with a mixed solvent of petroleum ether:ethyl acetate ratio of 5:1 as the eluent, collect the eluate portion of all products detected, and obtain 70.8 mg of the product after rotary evaporation to remove the solvent. Yield 81%, Dr value 6:1.

[0020] White solid, mp: 191-192℃. 1 H NMR (300MHz, CDCl 3 ): δ7.83(m, 1H), 7.62(d, J=6.2Hz, 1H), 7.49-7.30(m, 3H), 7.29-7.15(4H, m), 7.05-6.86(m, 4H), 6.57(m, 1H), 4.75(d, J=15.2Hz, 1H), 4.34(d, J=15.3Hz, 1H), 3.37(d, J=17.3Hz, 1H), 2.93(d, J=17.4 Hz, 1H). 13 C NMR (...

Embodiment 2

[0021] Example 2: the reaction of 2-(1-benzyl-2-oxoindol-3-yl)acetic acid and 2,2,2,4'-tetrafluoroacetophenone

[0022] 56.2 mg (0.2 mmol) of 2-(1-benzyl-2-oxoindol-3-yl) acetic acid, 57.6 mg (0.3 mmol) of 2,2,2,4'-tetrafluoroacetophenone, such as N shown in formula III, N'-carbonyldiimidazole 39mg (0.24mmol), cesium carbonate 130mg (0.4mmol), p-toluenesulfonic acid 34.4mg (0.2mmol) and dichloromethane 2mL are placed in 25mL two-necked bottle, at 25 The reaction solution was reacted at ℃ for 4 h, the reaction solution was concentrated, and eluted by column chromatography using a mixed solvent of petroleum ether:ethyl acetate ratio of 5:1 as the eluent, and the eluate part of all detected products was collected and spun After distilling off the solvent, 86 mg of the product was obtained, the yield was 95%, and the Dr value was 2:1.

[0023] White solid, mp: 209-211℃. 1 H NMR (300MHz, CDCl 3 ): δ8.04-7.67(m, 2H), 7.49(m, 1H), 7.40-7.29(m, 4H), 7.15-7.00(m, 4H), 6.90-6.35(m, 2...

Embodiment 3

[0024] Example 3: Reaction of 2-(1-benzyl-2-oxoindol-3-yl)acetic acid and 4'-bromo-2,2,2-trifluoroacetophenone

[0025] 56.2 mg (0.2 mmol) of 2-(1-benzyl-2-oxoindol-3-yl) acetic acid, 75.5 mg (0.3 mmol) of 4'-bromo-2,2,2-trifluoroacetophenone 39 mg (0.24 mmol) of N, N'-carbonyldiimidazole, 130 mg (0.4 mmol) of cesium carbonate, 34.4 mg (0.2 mmol) of p-toluenesulfonic acid and 2 mL of dichloromethane were placed in a 25 mL two-necked bottle as shown in formula III, Reacted at 25°C for 4h, concentrated the reaction solution, and eluted by column chromatography with a mixed solvent of petroleum ether:ethyl acetate ratio of 5:1 as the eluent, and collected the eluate portion of all detected products , and the solvent was removed by rotary evaporation to obtain 92 mg of the product with a yield of 90% and a Dr value of 3:1.

[0026] White solid, mp: 225-227℃. 1 H NMR (300MHz, CDCl 3): δ7.78-7.58(m, 3H), 7.41(t, J=7.7Hz, 1H), 7.32-7.28(m, 3H), 7.20(t, J=7.7Hz, 1H), 7.00-6.90( m,...

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Abstract

The invention relates to the field of organic chemistry and in particular relates to a spiro-oxindole gamma-butyrolactone compound IV. The spiro-oxindole gamma-butyrolactone compound IV is prepared by taking an acid shown as a formula I and acetone shown as a formula II as raw materials, and taking dichloromethane as a solvent in the presence of N,N'-carbonyl diimidazole shown as a formula III, p-toluene sulfonic acid and cesium carbonate, reacting at 25 DEG C for 4h, concentrating a reaction solution, eluting by column chromatography, collecting eluting solution parts of all detected products and carrying out rotary evaporation to remove the solvent. The invention further provides a spiro-oxindole gamma-butyrolactone compound VI which is prepared by taking the acid shown as the formula I and N-substituted isatin shown as a formula V as raw materials, and taking tetrahydrofuran as a solvent in the presence of 2-(7-benzotriazole oxide)-N,N,N',N'-tetramethyluronium hexafluorophosphate and triethylamine, reacting at 0 DEG C for 6h, concentrating a reaction solution, eluting by column chromatography, collecting eluting solution parts of all detected products and carrying out rotary evaporation to remove the solvent. A synthesis method has the advantages of relatively good yield, wide substrate applicable range, simplicity and convenience for operation, moderate reaction, convenience for post-treatment and the like.

Description

[0001] (1) Technical field [0002] The invention relates to a method for synthesizing spirocyclic indole gamma-butyrolactone compounds, which belongs to the field of organic chemistry synthesis methodology. [0003] (2) Background technology [0004] The spiro-epoxy indole structure widely exists in natural products and drug molecules with various biological activities (Eur. J. Org. Chem. 2003, 2209; Mol. Divers. 2016, 299.). γ-butyrolactone is also an important molecular module with various bioactive drug molecules. [0005] Spiroepoxindole γ-butyrolactones are an important subtype of spiroepoxindole derivatives, but their synthesis and research are few. Therefore, it is very necessary to develop a general and convenient method for preparing such compounds. [0006] (3) Contents of the invention [0007] The object of the present invention is to provide a method for synthesizing spirooxindole γ-butyrolactone compounds with simple operation, mild reaction conditions, high y...

Claims

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Application Information

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IPC IPC(8): C07D491/107C07D491/20
CPCC07D491/107C07D491/20
Inventor 杜鼎曹京董书顶
Owner CHINA PHARM UNIV
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