Methodology for the Synthesis of Substituted 1,3-Oxazoles

Abstract

The halogen dance isomerization is a facile and preparatively effective pathway for the synthesis of 2,4,5-trisubstituted 1,3-oxazoles.

oxazoles - halogen dance rearrangement - alkylation

References and Notes

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<A NAME="RD37509ST-21">21</A>

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).

<A NAME="RD37509ST-22">22</A>

Yields of Table  [¹] are provided for purified products which were characterized by ^¹H NMR and ^¹³C NMR spectroscopy, IR spectroscopy, and HRMS analysis.