Synfacts 2011(5): 0486-0486  
DOI: 10.1055/s-0030-1259842
Synthesis of Heterocycles
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of 2-Halo-3-carboxyindoles

Contributor(s): Victor Snieckus, Matthew O. Kitching
A. R. Kunzer*, M. D. Wendt
Abbott Laboratories, Abbott Park, USA
Further Information

Publication History

Publication Date:
15 April 2011 (online)

Significance

Reported is the synthesis of 2-halo-3-carboxyindoles (2, 4) via the cesium carbonate mediated cyclization of 1,1-dihalovinyl anilines (1, 3). Initial experimentation established the pre-eminence of polar solvents for this transformation. Further optimization revealed that although water is tolerated in the process, anhydrous reaction conditions led to greatly enhanced rates of reaction. In addition, base screens demonstrated the importance of base solubility to the process. The reaction afforded the desired products (2, 4) in yields generally higher than 65%. Only the readily oxidized vinylanisidine gave the desired product in low (40%) yield. Notably, the analogous cyclizations of 1,1-dibromovinyl phenols and thiophenols are reported to fail. Furthermore, N-substituted anilines (5) do not give the corresponding indoles, instead affording oxazinone 6 in low yield.