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DOI: 10.1055/s-2004-820015
A Practical Synthesis of 2-Aryl-Indole-6-carboxylic Acids
Publication History
Publication Date:
24 February 2004 (online)
Abstract
A practical synthesis of 2-aryl-indole-6-carboxylic acids was developed via a sequence consisting of SNAr reaction, reductive cyclization, hydrolysis and decarboxylation. This process is efficient in terms of operational simplicity, cost effectiveness and is amenable to large scale production.
Key words
indole - SNAr reaction - reductive cyclization
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References
The spectral data of compounds 4 and 5 were obtained from the NMR of the mixture. Not all the coupling constants could be calculated due to overlapping signals. Compound 4: 1H NMR (400 MHz, DMSO-d 6): δ = 8.59 (d, J = 1.3 Hz, 1 H), 8.28 (d, J = 1.3 Hz, 1 H), 8.06 (d, J = 4.5 Hz, 1 H), 7.88 (m, 1 H), 7.86 (m, 1 H), 7.69 (dd, J = 1.3, 4.5 Hz, 1 H), 7.67 (dd, J = 1.3, 7.8 Hz, 1 H), 6.83 (s, 1 H), 4.27 (q, 2 H), 1.25 (t, 3 H). Compound 5: 1H NMR (400 MHz, DMSO-d 6): δ = 8.50-7.20 (m, 3 H), 4.09 (s, 2 H), 4.17 (q, 2 H), 1.25 (t, 3 H). Compound 6: MS: calcd 267.24; found: (M + 1) 268.27.
12The use of fluoride as a better leaving group for the SNAr reaction was evaluated but showed little improvement. The less expensive and commercially available aryl chloride was preferred in this study.