Dihydropyrrole derivates and method for preparing intermediate pyrrolidine

A technology of tetrahydropyrrole and dihydropyrrole, which is applied in the direction of organic chemistry, can solve the problems of unsuitability for industrialization, inconvenient operation, site selectivity and low yield, and achieve high reaction yield and safe and simple operation.

Inactive Publication Date: 2009-04-29
EAST CHINA NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, this method has problems such as regioselectivity and low yield, and the raw material is not easy to obtain, so it needs to be prepared separately
One of the methods for preparing the raw material is to obtain the raw material in two steps, but the strong acidic and corrosive reagent perchloric acid is used, and it needs to be reacted at high temperature, so there is a great risk of explosion, which is v

Method used

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  • Dihydropyrrole derivates and method for preparing intermediate pyrrolidine
  • Dihydropyrrole derivates and method for preparing intermediate pyrrolidine
  • Dihydropyrrole derivates and method for preparing intermediate pyrrolidine

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Experimental program
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Effect test

Embodiment 1

[0029] Dissolve (E)-2-oxo-4-p-chlorophenyl-3-butenoic acid methyl ester (2mmol), aniline (2.4mmol) and rhodium acetate (0.02mmol) in dichloromethane (12mL) to form For the reaction system, dissolve methyl phenyldiazoacetate (2.4mmol) in 5mL of dichloromethane to form a solution, and slowly add the solution formed by dissolving methyl phenyldiazoacetate in dichloromethane under reflux within 1 hour into the reaction system. After the dropwise addition, the solvent was evaporated under reduced pressure to obtain a crude product, which was subjected to column chromatography (ethyl acetate:petroleum ether=1:40~1:10) to obtain the corresponding intermediate tetrahydropyrrole derivative, and the yield was was 78%.

[0030] The intermediate tetrahydropyrrole derivative (1mmol) was mixed with toluene (15mL), citric acid monohydrate (0.2mmol) was added, water was carried through the water separator under reflux for 3 hours, cooled to room temperature, and the solvent was evaporated un...

Embodiment 2

[0032] Dissolve (E)-methyl 2-oxo-4-m-bromophenyl-3-butenoate (2mmol), aniline (2.4mmol) and rhodium acetate (0.02mmol) in dichloromethane (12mL) to form For the reaction system, methyl phenyldiazoacetate (2.4 mmol) was dissolved in 5 mL of dichloromethane to form a solution, and the solution was slowly added dropwise to the reaction system within 1 hour under reflux. After the dropwise addition, the solvent was evaporated under reduced pressure to obtain a crude product, which was subjected to column chromatography (ethyl acetate:petroleum ether=1:40~1:10) to obtain the corresponding intermediate tetrahydropyrrole derivative, and the yield was was 73%.

[0033] The intermediate tetrahydropyrrole derivative (1mmol) was mixed with toluene (15mL), and citric acid monohydrate (0.2mmol) was added, and the reaction system was refluxed with water for 4 hours through a water separator, cooled to room temperature, and depressurized The solvent was evaporated to obtain a crude product,...

Embodiment 3

[0035]Dissolve (E)-methyl 2-oxo-4-p-nitrophenyl-3-butenoate (2mmol), aniline (2.4mmol) and rhodium acetate (0.02mmol) in dichloromethane (12mL) To form a reaction system, methyl phenyldiazoacetate (2.4 mmol) was dissolved in 5 mL of dichloromethane to form a solution, and the solution was slowly added dropwise to the reaction system within 1 hour under reflux. After the dropwise addition, the solvent was evaporated under reduced pressure to obtain a crude product, which was subjected to column chromatography (ethyl acetate:petroleum ether=1:40~1:10) to obtain the corresponding intermediate tetrahydropyrrole derivative, and the yield was was 86%.

[0036] The intermediate tetrahydropyrrole derivative (1mmol) was mixed with toluene (15mL), and citric acid monohydrate (0.2mmol) was added, and the reaction system was refluxed with water for 3 hours through a water separator, cooled to room temperature, and depressurized The solvent was evaporated to obtain a crude product, which ...

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Abstract

The invention discloses a method for preparing a dihydropyrrole derivative and an intermediate pyrrolidine thereof, and relates to the preparation of the pyrrolidine and the dihydropyrrole derivative. Firstly, a diazocompound, amine, beta, gamma-unsaturated-alpha-keto ester with the mol ratio of 1.2 to 1.2 to 1 to 0.01 are weighed as raw materials, metal Lewis acid is taken as a catalyst, the diazocompound is decomposed to form metal carbine through a three-component tandem reaction under the catalysis of the metal Lewis acid, ammonium ylide obtained by in-situ formation of the metal carbine and the amine is captured by the beta, gamma-unsaturated-alpha-keto ester through the 1, 4-addition mode, then a corresponding intermediate pyrrolidine derivative is obtained through intra-molecular condensation, finally the pyrrolidine derivative is mixed with an organic solvent, then an organic acid catalyst is added to form a reaction system, and then the corresponding dihydropyrrole derivative is obtained through the water entrainment of a water segregator. The method has the advantages of high atom economy, high efficiency, high yield and so on, and has safe and simple operation. The prepared pyrrolidine and the dihydropyrrole derivative are widely applied to the field of pharmaceutical and chemical industries.

Description

technical field [0001] The invention discloses a method for preparing dihydropyrrole derivatives and tetrahydropyrrole intermediates thereof, and relates to the preparation of tetrahydropyrrole and dihydropyrrole derivatives. The invention belongs to the technical field of chemical synthesis and medicine. Background technique [0002] Tetrahydropyrrole and dihydropyrrole derivatives are important skeleton structures for natural products and synthetic drugs, such as Glycopyrronium Bromide (Glycopyrronium Bromide) for anti-gastric acid and anti-ulcer drug, Kainic Acid (Kainic Acid) for anthelmintics and antibiotics Drug structures such as lincomycin and lindamycin all have such skeleton structures. However, dihydropyrrole derivatives can be easily reduced to corresponding tetrahydropyrrole derivatives or generated through aromatization, and their derivatives serve as key intermediates in the total synthesis of many natural products (J.Am 2005, 127, 5342; J. Am. Chem. Soc. 20...

Claims

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Application Information

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IPC IPC(8): C07D207/277C07D207/16
Inventor 胡文浩朱映光翟昌伟张娜杨琍苹
Owner EAST CHINA NORMAL UNIVERSITY
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