Synlett 2010(4): 591-594  
DOI: 10.1055/s-0029-1219374
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Methodology for the Synthesis of Substituted 1,3-Oxazoles

David R. Williams*, Liangfeng Fu
Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, IN 47405-7102, USA
Fax: +1(812)8558300; e-Mail: williamd@indiana.edu;
Further Information

Publication History

Received 22 December 2009
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.

    References and Notes

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21

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).

22

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