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DOI: 10.1055/s-0029-1219374
Methodology for the Synthesis of Substituted 1,3-Oxazoles
Publication History
Publication Date:
08 February 2010 (online)
Abstract
The halogen dance isomerization is a facile and preparatively effective pathway for the synthesis of 2,4,5-trisubstituted 1,3-oxazoles.
Key words
oxazoles - halogen dance rearrangement - alkylation
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References and Notes
Preparation of
Starting Oxazole 1
A CH2Cl2 solution
of 2-phenylthio-1,3-oxazole (1.0 equiv) and anhyd Et3N
(1.5 equiv) was stirred at 0 ˚C, and bromine (1.5
equiv) in CH2Cl2 (1:1 by volume) was introduced
by slow dropwise addition. The reaction mixture was allowed to warm
slowly to 22 ˚C, and stirring was continued overnight. The
reaction was quenched with aq sat. NaHCO3 and was extracted
with CH2Cl2. Organic phases were combined
and washed with aq NaHSO3 and then dried over anhyd Na2SO4. Evaporation
of solvent and flash silica gel chromatography (8:1 hexane-EtOAc)
provided 5-bromo-2-phenylthio-1,3-oxazole (75% yield).
Yields of Table [¹] are provided for purified products which were characterized by ¹H NMR and ¹³C NMR spectroscopy, IR spectroscopy, and HRMS analysis.