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tions the reaction mixture remained fully homogeneous but no
full conversion from bromo oxazole 6c to azido oxazole 7c was
achieved (78%), which prevented the formation of the final
product in a pure form.
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Conclusion
We have developed a continuous-flow protocol for the prepara-
tion of 2-(azidomethyl)oxazoles. The procedure consists of a
three-step sequential synthesis combining an initial thermolysis
of the starting vinyl azide to form an azirine intermediate, fol-
lowed by reaction with bromoacetyl bromide to generate the
oxazole moiety, and a final nucleophilic halide displacement
with NaN3 to give the desired product. After optimization of all
individual steps in batch and continuous-flow mode, the com-
plete sequence has been integrated in a single continuous-flow
reactor, in which the vinyl azide is fed as substrate and the final
2-(azidomethyl)oxazole is formed and collected from the
reactor output. The process avoids the isolation and handling of
the unstable 2-(bromomethyl)oxazole intermediates, thus
circumventing decomposition problems. The continuous reactor
has been tested for three different vinyl azide substrates. Good
results were obtained for compounds 7a and 7b, while for 7c
dilution was necessary to avoid clogging of the reactor.
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Supporting Information
16.Bresciani, S.; Tomkinson, N. C. O. Heterocycles 2014, 89, 2479–2543.
Supporting Information File 1
Experimental procedures and copies of the NMR spectra
for all isolated compounds.
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Acknowledgements
C.O.K acknowledges the Science without Borders program
(CNPq, CAPES) for a “Special Visiting Researcher” fellow-
ship. T.A.S. and N.S.S. are grateful to CAPES (Coordenação de
Aperfeiçoamento de Pessoal de Nível Superior, Brazil) for
fellowships. Special thanks are due to CEBIME (Laboratorio
Central de Biologia Molecular e Estrutural, UFSC, Brazil) for
providing the mass spectra.
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ORCID® iDs
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