Synthesis 2012; 44(16): 2519-2526
DOI: 10.1055/s-0031-1290809
special topic
© Georg Thieme Verlag Stuttgart · New York

An Efficient Synthesis of 2-(Trifluoromethyl)-2H-[1,3]oxazino[2,3-a]isoquinolines via a Three-Component Cascade Approach Using a Continuous-Flow Microreactor

Ming Lei*
a  Department of Chemistry, Zhejiang University, 310027 Hangzhou, P. R. of China, Fax: +86(571)87951895   Email: leiming@zju.edu.cn
b  Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Zhejiang University Medical PET Center, 310009 Hangzhou, P. R. of China, Fax: +86(571)87767188   Email: hzhang21@gmail.com
,
Wan Tian
a  Department of Chemistry, Zhejiang University, 310027 Hangzhou, P. R. of China, Fax: +86(571)87951895   Email: leiming@zju.edu.cn
,
Ruijun Hu
a  Department of Chemistry, Zhejiang University, 310027 Hangzhou, P. R. of China, Fax: +86(571)87951895   Email: leiming@zju.edu.cn
,
Wei Li
a  Department of Chemistry, Zhejiang University, 310027 Hangzhou, P. R. of China, Fax: +86(571)87951895   Email: leiming@zju.edu.cn
,
Hong Zhang*
b  Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Zhejiang University Medical PET Center, 310009 Hangzhou, P. R. of China, Fax: +86(571)87767188   Email: hzhang21@gmail.com
c  Department of Nuclear Medicine, Second Affiliated Hospital of Zhejiang University, School of Medicine, 310009 Hangzhou, P. R. of China
› Author Affiliations
Further Information

Publication History

Received: 18 February 2012

Accepted: 05 March 2012

Publication Date:
08 May 2012 (eFirst)

Abstract

The three-component reaction between an isoquinoline, a dialkyl acetylenedicarboxylate and 2,2,2-trifluoro-1-phenyleth­anone involving a 1,4-dipolar cycloaddition cascade approach is developed using a continuous-flow microreactor. The reaction conditions (solvent, flow rate and temperature) are optimized leading to the synthesis 2-(trifluoromethyl)-2H-[1,3]oxazino[2,3-a]isoquinoline derivatives in 79-83% isolated yields, whilst eliminating the formation of 11bH-pyrido[2,1-a]isoquinoline-1,2,3,4-tetracarboxylate by-products. The continuous-flow method is also applied to similar reactions using aromatic aldehydes as the carbonyl component.

 
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