Quinolines from the Cyclocondensation of Isatoic Anhydride With Ethyl Acetoacetate: Preparation of Ethyl 4-Hydroxy-2-Methylquinoline-3-Carboxylate and Derivatives

Authors

Nicholas JentschFollow
Jared D. Hume, University of Southern MississippiFollow
Emily B. Crull, University of Southern Mississippi
Samer M. Beauti, University of Southern MississippiFollow
Amy H. Pham, University of Southern Mississippi
Julie A. Pigza, The University of Southern MississippiFollow
Jacques Kessl, University of Southern MississippiFollow
Matthew G. Donahue, University of Southern MississippiFollow

Document Type

Article

Publication Date

9-28-2018

Department

Chemistry and Biochemistry

Abstract

A convenient two-step synthesis of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate derivatives has been developed starting from commercially available 2-aminobenzoic acids. In step 1, the anthranilic acids are smoothly converted to isatoic anhydrides using solid triphosgene in THF. In step 2, the anhydride electrophiles are reacted with the sodium enolate of ethyl acetoacetate, generated from sodium hydroxide, in warm N,N-dimethylacetamide resulting in the formation of substituted quinolines. A degradation–build-up strategy of the ethyl ester at the 3-position allowed for the construction of the α-hydroxyacetic acid residue required for the synthesis of key arylquinolines involved in an HIV integrase project.

Comments

Published by Beilstein Journal of Organic Chemistry at 10.3762/bjoc.14.229.

Publication Title

Journal of Organic Chemistry

Volume

14

First Page

2529

Last Page

2536

Recommended Citation

Jentsch, N., Hume, J. D., Crull, E. B., Beauti, S. M., Pham, A. H., Pigza, J. A., Kessl, J., Donahue, M. G. (2018). Quinolines from the Cyclocondensation of Isatoic Anhydride With Ethyl Acetoacetate: Preparation of Ethyl 4-Hydroxy-2-Methylquinoline-3-Carboxylate and Derivatives. Journal of Organic Chemistry, 14, 2529-2536.
Available at: https://aquila.usm.edu/fac_pubs/15557