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Synthesis 2020; 52(22): 3480-3484
DOI: 10.1055/s-0040-1707344
DOI: 10.1055/s-0040-1707344
paper
Scalable Synthesis of 3-Ethyl-4-methyl-1,5-dihydro-2H-pyrrol-2-one: An Important Building Block of the Antidiabetic Drug Glimepiride
A.A.P. and A.L.K. thank the University Grants Commission (UGC), New Delhi and N.B.P. thanks the Council of Scientific and Industrial Research (CSIR), New Delhi for the award of research fellowships. The authors thank CSIR, New Delhi for financial support as part of the XII Year Plan Programme under title ORIGIN (CSC-0108) and ACT (CSC-0301).Further Information
Publication History
Received: 18 February 2020
Accepted after revision: 25 June 2020
Publication Date:
04 August 2020 (online)
Abstract
A four-step, practical, and easily scalable synthesis of 3-ethyl-4-methyl-1,5-dihydro-2H-pyrrol-2-one, an important building block of the antidiabetic drug glimepiride, has been accomplished. Key features are the synthesis of 3-methyl-4-hydroxy-2-butenolide in water and triflic acid mediated N-benzyl lactam N-deprotection. The main advantages of this process are the scalable synthetic route and decreased number of reaction steps, which paves the way for the industrial-scale synthesis of 3-ethyl-4-methyl-1,5-dihydro-2H-pyrrol-2-one.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707344.
- Supporting Information
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References
- 1 IDF Diabetes Atlas, 8th ed. International Diabetes Federation; Brussels: 2017
- 2a Gurjar MK, Joshi RA, Chaudhuri SR, Joshi SV, Barde AR, Gediya LK, Ranade PV, Kadam SM, Naik SJ. Tetrahedron Lett. 2003; 44: 4853
- 2b Tanwar DK, Vaghela RS, Gill MS. Synlett 2017; 28: 2495
- 3a Davis SN. J. Diabetes Complications 2004; 18: 367
- 3b Massi-Benedetti M. Clin. Ther. 2003; 25: 799
- 3c Campbell RK. Ann. Pharmacother. 1998; 32: 1044
- 4 Sabido PM. G, Lightner DA. Monatsh. Chem. 2014; 145: 775
- 5a Bishop JE, Nagy JO, O’Connell JF, Rapoport H. J. Am. Chem. Soc. 1991; 113: 8024
- 5b Tipton AK, Lightner DA. Monatsh. Chem. 1999; 130: 425
- 5c Coffin AR, Roussell MA, Tserlin E, Pelkey ET. J. Org. Chem. 2006; 71: 6678
- 5d Chavan SP, Pathak AB, Pawar KP. Synthesis 2015; 47: 955
- 6a Chepelev LL, Beshara CS, MacLean PD, Hatfield GL, Rand AA, Thompson A, Wright JS, Barclay LR. C. J. Org. Chem. 2006; 71: 22
- 6b Pasquier C, Gossauer A, Keller W, Kratky C. Helv. Chim. Acta 1987; 70: 2098
- 6c Contreras-García E, Martínez-López D, Alonso CA, Lozano C, Torres C, Rodríguez MA, Campos PJ, Sampedro D. Eur. J. Org. Chem. 2017; 4719
- 7 Bourguignon JJ, Wermuth CG. J. Org. Chem. 1981; 46: 4889
- 8 Awuah E, Capretta A. J. Org. Chem. 2011; 76: 3122
- 9 Humphries PS, Bersot R, Kincaid J, Mabery E, McCluskie K, Park T, Renner T, Riegler E, Steinfeld T, Turtle ED, Wei Z.-L, Willis E. Bioorg. Med. Chem. Lett. 2018; 28: 293