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Synlett 2018; 29(15): 1989-1994
DOI: 10.1055/s-0037-1610228
letter
© Georg Thieme Verlag Stuttgart · New York

Efficient Preparation of Cyclic α-Alkylidene β-Oxo Imides by Using a Flow Microreactor System

Katsuhiro Komuro
a   Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555, Japan   Email: mnakada@waseda.jp
,
Aiichiro Nagaki
b   Department of Synthetic and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto, 615-8510, Japan
,
Hiroki Shimoda
a   Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555, Japan   Email: mnakada@waseda.jp
,
Masahiro Uwamori
a   Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555, Japan   Email: mnakada@waseda.jp
,
Jun-ichi Yoshida
b   Department of Synthetic and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto, 615-8510, Japan
,
Masahisa Nakada*
a   Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555, Japan   Email: mnakada@waseda.jp
› Author AffiliationsThis work was financially supported in part by JSPS KAKENHI Grant Number 15H05841 in Middle molecular strategy and a Waseda University Grant for Special Research Projects.
Further Information

Publication History

Received: 29 June 2018

Accepted after revision: 10 July 2018

Publication Date:
28 August 2018 (online)

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Abstract

Successful transformations of 3-iodo-1-methyl-5,6-dihydropyridin-2(1H)-one into its derivatives by a halogen–lithium exchange and subsequent reactions in a flow microreactor system are described. The methylation of the organolithium compound generated from 3-iodo-1-methyl-5,6-dihydropyridin-2(1H)-one in the flow microreactor system afforded the desired methylated product in 68% yield, whereas the yield of the corresponding batch reaction was 23%. This superiority of the flow microreactor system was further emphasized in the reaction of the organolithium compound with methoxycarbonyl isocyanate, which gave the desired imide in 78% yield by using the flow microreactor system whereas the yield of the corresponding batch reaction was only 2%. The established flow microreactor system was also effectively used for the reaction of the organolithium compound with phenyl isocyanate to afford the desired product in 52% yield.

Key words

flow microreactor system - halogen–lithium exchange reaction - lithiation - imides - isocyanates - methylation

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610228.
  • Supporting Information
 

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