Synthesis
General procedure for the synthesis of 2-amino-5-ethylbenzoic acid from 5-ethylindoline-2,3-dione: Sodium hydroxide (6.5 g, 162.5 mmol) was dissolved in distilled water (52 mL) and cooled to below 30 °C. Subsequently, 5-ethylindoline-2,3-dione (9.6 g, 54.8 mmol) was slowly added with continuous stirring. The reaction bath was further cooled to below 15 °C and 30% hydrogen peroxide solution (15.6 g) was slowly added dropwise while controlling the reaction temperature between 15-20 °C. After the dropwise addition, the reaction temperature was maintained at 15-20 °C to continue the reaction for 1 hour. Subsequently, the pH of the reaction solution was adjusted to 5-6 by slowly adding glacial acetic acid dropwise, at which time a yellow solid precipitated. The precipitated solid was collected by filtration and washed with a small amount of cold water and then dried. The crude product was recrystallized by ethanol/water (1:1, v/v) solvent mixture to give 3.4 g of yellow solid product in 38% yield.
References
[1] Chemistry Letters, 2009, vol. 38, # 3, p. 200 - 201
[2] Patent: CN104803927, 2017, B. Location in patent: Paragraph 0109; 0113; 0114
[3] Il Farmaco; edizione scientifica, 1968, vol. 23, # 1, p. 3 - 15
[4] Patent: US2004/167128, 2004, A1. Location in patent: Page 22
[5] Patent: WO2003/97641, 2003, A2. Location in patent: Page/Page column 67
