Synthesis
The general procedure for the synthesis of 5-chloroindole-2-carboxylic acid from ethyl 5-chloroindole-2-carboxylate was as follows: 111.5 g of ethyl 5-chloroindole-2-carboxylate was dissolved in a mixture of 31.25 g of 96% sodium hydroxide, 183 ml of methanol, and 183 ml of water, and was heated and refluxed for 1 hour. After the reaction was completed, the reaction solution was cooled to 40 °C, and 10% hydrochloric acid was slowly added dropwise to adjust the pH to 3-4. After the reaction solution was completely cooled, the precipitate was collected by filtration to obtain 90.1 g of off-white 5-chloroindole-2-carboxylic acid in 92.5% yield, and the purity of the product was ≥96% by high performance liquid chromatography (HPLC).
References
[1] Chemical Biology and Drug Design, 2017, vol. 90, # 1, p. 64 - 82
[2] Patent: CN104402795, 2017, B. Location in patent: Paragraph 0045; 0048
[3] European Journal of Medicinal Chemistry, 2011, vol. 46, # 7, p. 3149 - 3157
[4] Advanced Synthesis and Catalysis, 2016, vol. 358, # 24, p. 3938 - 3942
[5] Journal of the Chemical Society, 1955, p. 3499,3502
