Синтез 3-арил-3-трифторометил-2,3-дигідро-1Н-піролізин-1-онів

• Date: 2019
• Main Authors: Melnykov, S. V., Tkachuk, V. M., Grozav, A. M., Gillaizeau, I., Sukach, V. A.
• Format: Article
• Language: Ukrainian
• Published: National University of Pharmacy 2019
• Subjects: естери 3-аміно-3-арил-4; 4; 4-трифторо-3-арилбутанової кислоти; 2; 5-диметокситетрагідрофуран; 3-арил-3-трифторометил-2; 3-дигідро-1Н-піролізин-1-они; бромід бору; циклоконденсація; 547.466 547.745 547.754
• Online Access: https://ophcj.nuph.edu.ua/article/view/ophcj.19.961
• Journal Title: Journal of Organic and Pharmaceutical Chemistry

Aim. To develop the efficient method for the synthesis of 3-aryl-3-trifluoromethyl-2,3-dihydro-1H-pyrrolizin-1-ones as promising scaffolds in design of bioactive compounds.Results and discussion. It has been shown that condensation of 3-amino-3-aryl-4,4,4-trifluorobutanoic acid methyl esters with 2,5-dimethoxytetrahydrofuran is a convenient synthetic approach to 4,4,4-trifluoro-3-aryl-3-(1H-pyrrol-1-yl)methylbutanoic acid methyl esters converted to 3-aryl-3-trifluoromethyl-2,3-dihydro-1H-pyrrolizin-1-ones by the intramolecular Friedel-Crafts reaction.Experimental part. By the interaction of 3-amino-3-aryl-4,4,4-trifluorobutanoic acid methyl esters with 2,5-dimethoxytetrahydrofuranin acetic acid at 70 оC 4,4,4-trifluoro-3-aryl-3-(1H-pyrrol-1-yl)methylbutanoic acid methyl esters were obtained and subsequently cyclized into 3-aryl-3-trifluoromethyl-2,3-dihydro-1H-pyrrolizin-1-ones upon treatment with boron tribromide in dichloromethane at room temperature. The structures of the compounds synthesized were confirmed by LCMS, IR and NMR (1H, 13C, 19F) spectroscopic methods.Conclusions. An efficient two step protocol for the synthesis of 3-aryl-3-trifluoromethyl-2,3-dihydro-1H-pyrrolizin-1-ones has been developed. It includes transformation of 3-amino-3-aryl-4,4,4-trifluorobutanoic acid methyl esters into the corresponding 3-(1H-pyrrol-1-yl) derivatives and their further intramolecular cyclization.