Synthesis
General method: synthesis of 2-(4-((tert-butoxycarbonyl)amino)phenyl)acetic acid (5). 4-Aminophenylacetic acid (4, 4 g, 26.46 mmol, 1 equiv) was dissolved in a solvent mixture of dioxane (52 mL) and water (52 mL). In a separate vessel, sodium carbonate (2.8 g, 26.42 mmol, 1 eq.) was dissolved in water (25 mL), stirred and cooled in an ice bath. The sodium carbonate solution was added to a solution of 4-aminophenylacetic acid followed by a one-time addition of di-tert-butyl dicarbonate (BOC-anhydride, 6.24 g, 28.59 mmol, 1.1 eq.). The reaction mixture was continued to be stirred at room temperature for 4 hours. After completion of the reaction, the dioxane was removed by distillation under reduced pressure. The cooled aqueous layer was covered with ethyl acetate and acidified with dilute KHSO4 solution to pH 4. Subsequent extraction with ethyl acetate was carried out and the organic layers were combined and purified by column chromatography (eluent ratio of ethyl acetate-hexane-acetic acid in 1:1:1 eluent ratio) to afford the target compound 5 (7.07 g, 94% yield) as a white solid.1H-NMR (300 MHz, CDCl3) The data were as follows: δ 7.29 (d, J = 8.40 Hz, 2H), 7.19 (d, J = 8.47 Hz, 2H), 3.70 (s, 1H), 3.58 (s, 2H), 1.52 (s, 9H).
References
[1] Journal of Medicinal Chemistry, 1998, vol. 41, # 13, p. 2361 - 2370
[2] Molecules, 2017, vol. 22, # 1,
[3] Patent: US6335445, 2002, B1. Location in patent: Page column 86-87
[4] Journal of Medicinal Chemistry, 2013, vol. 56, # 1, p. 254 - 263
[5] Patent: WO2014/85545, 2014, A1. Location in patent: Page/Page column 52; 53
