Synthesis
The general procedure for the synthesis of 5-bromo-1H-indole-7-carboxylic acid from methyl 5-bromoindole-7-carboxylate was as follows: methyl 5-bromo-1H-indole-7-carboxylate (5 g, 19.7 mmol) was dissolved in methanol (200 mL), followed by the addition of an aqueous solution (10 mL) of lithium hydroxide (0.99 g, 41 mmol). The reaction mixture was heated to reflux and kept for 50 hours. Upon completion of the reaction, methanol was removed by distillation under reduced pressure. The residue was acidified by adding 2M aqueous hydrochloric acid solution to the residue, followed by filtration to collect the precipitate precipitated. The resulting solid was dried in a heated vacuum drying oven to give 4.7 g (99% yield) of the target product 5-bromo-1H-indole-7-carboxylic acid as a beige solid. The product was characterized by 1H NMR (400 MHz, DMSO-D6): δ 6.54 (dd, J = 2.0, 3.2 Hz, 1H), 7.42 (t, J = 2.8 Hz, 1H), 7.77 (d, J = 2.0 Hz, 1H), 8.03 (d, J = 1.8 Hz, 1H), 11.27 (s, 1H), 13.1-13.7 (bs, 1H). Mass spectrometry analysis showed m/z of 238/240 (ratio 1:1, [M-1]-) and retention time (Rt) of 3.41 min.
References
[1] Patent: WO2007/62318, 2007, A2. Location in patent: Page/Page column 39
[2] Patent: WO2008/118724, 2008, A1. Location in patent: Page/Page column 70
[3] Patent: US2006/30613, 2006, A1. Location in patent: Page/Page column 22
[4] Patent: WO2006/34317, 2006, A2. Location in patent: Page/Page column 73-74
[5] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 8, p. 2255 - 2258
