Development of a continuous flow synthesis of propranolol: tackling a competitive side reaction
作者： Sonia De Angelis , Paolo Celestini , Rosa Purgatorio , Leonardo Degennaro , Gabriele Rebuzzini
DOI: 10.1007/S41981-019-00047-8
关键词:
摘要: This work reports the preparation of propranolol according to a flow process. Propranolol has been prepared paying attention tackle formation by-product tertiary amine, resulting from an additional ring opening starting epoxide. Remarkably, use catalytic amount water resulted beneficial for yield and purity desired propranolol, substantially reducing amine byproduct. The high concentration solutions allowed productivity several grams/h.
springer.com
sci-hub.se 参考文章(23)
Matthew W. Bedore, Nikolay Zaborenko, Klavs F. Jensen, Timothy F. Jamison, Aminolysis of Epoxides in a Microreactor System: A Continuous Flow Approach to β-Amino Alcohols Organic Process Research & Development. ,vol. 14, pp. 432- 440 ,(2010) , 10.1021/OP9003136
A. F. Crowther, L. H. Smith, Beta-adrenergic blocking agents. II. Propranolol and related 3-amino-1-naphthoxy-2-propanols. Journal of Medicinal Chemistry. ,vol. 11, pp. 1009- 1013 ,(1968) , 10.1021/JM00311A021
I. Vilotijevic, T. F. Jamison, Epoxide-Opening Cascades Promoted by Water Science. ,vol. 317, pp. 1189- 1192 ,(2007) , 10.1126/SCIENCE.1146421
Michael T. Cox, Stuart E. Jaggers, Geraint Jones, Linked Aryl Aryloxypropanolamines as a new class of lipid catabolis agents. Journal of Medicinal Chemistry. ,vol. 21, pp. 182- 188 ,(1978) , 10.1021/JM00200A008
Carl Kaiser, Timothy Jen, Eleanor Garvey, Wayne D. Bowen, Donald F. Colella, Joe R. Wardell, Adrenergic agents. 4. Substituted phenoxypropanolamine derivatives as potential beta-adrenergic agonists. Journal of Medicinal Chemistry. ,vol. 20, pp. 687- 692 ,(1977) , 10.1021/JM00215A014
Claire Tacon, Eric M. Guantai, Peter J. Smith, Kelly Chibale, Synthesis, biological evaluation and mechanistic studies of totarol amino alcohol derivatives as potential antimalarial agents. Bioorganic & Medicinal Chemistry. ,vol. 20, pp. 893- 902 ,(2012) , 10.1016/J.BMC.2011.11.060
Tomoya Nobuta, Guozhi Xiao, Diego Ghislieri, Kerry Gilmore, Peter H. Seeberger, Continuous and convergent access to vicinyl amino alcohols. Chemical Communications. ,vol. 51, pp. 15133- 15136 ,(2015) , 10.1039/C5CC06093A
Christopher J. Morten, Jeffery A. Byers, Timothy F. Jamison, Evidence That Epoxide-Opening Cascades Promoted by Water Are Stepwise and Become Faster and More Selective After the First Cyclization Journal of the American Chemical Society. ,vol. 133, pp. 1902- 1908 ,(2011) , 10.1021/JA1088748
Shivani, Brahmam Pujala, Asit K. Chakraborti, Zinc(II) perchlorate hexahydrate catalyzed opening of epoxide ring by amines: applications to synthesis of (RS)/(R)-propranolols and (RS)/(R)/(S)-naftopidils. Journal of Organic Chemistry. ,vol. 72, pp. 3713- 3722 ,(2007) , 10.1021/JO062674J
Simona Bonollo, Daniela Lanari, Luigi Vaccaro, Ring-Opening of Epoxides in Water European Journal of Organic Chemistry. ,vol. 2011, pp. 2587- 2598 ,(2011) , 10.1002/EJOC.201001693