Dihydropyrrole derivates and method for preparing intermediate pyrrolidine

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...

AI Technical Summary

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 very unfavorable for operation and industrialization (Angew.Chem., Int.Ed.1964, 3, 135); the second method uses imine, acid chloride and highly toxic gas carbon monoxide as raw materials, and obtains under palladium catalysis. Obviously, this method uses highly toxic gas carbon monoxide , brings great inconvenience to the operation, and is also not suitable for industrialization (J.Am.Chem.Soc.2003, 125, 1474)

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