Synthesis of 2-[(carboxymethyl)amino]benzoic acid (Intermediate-32): to a 500 mL two-necked RB flask equipped with a magnetic stirrer, o-aminobenzoic acid (20 g, 145 mmol) was added dropwise to a stirred solution of K2CO3 (83 g, 602 mmol) in water (140 mL), followed by chloroacetic acid (13.7 g, 145 mmol) dropwise under N2 atmosphere at room temperature for about 30 min. , 145 mmol) for about 30 minutes at room temperature under N2 atmosphere. The reaction material was then heated at 90C for 16 hours. After the reaction material was cooled to room temperature, the pH of the reaction material was adjusted to 4-5 using citric acid. the solids were then filtered and dried in a vacuum oven at 70C for 12 hours to produce Intermediate-32 (23 g) as a light brown solid.
Synthesis of N,O-1,3-diacetylindole (Intermediate-33): To a 500 mL two-necked RB flask equipped with a magnetic stirrer, acetic anhydride (110 mL, 1200 mmol) was slowly added to a stirred solution of triethylamine (170 mL, 1242 mmol) and Intermediate-32 (23 g, 117 mmol) at 0 C under an N2 atmosphere. 1200 mmol). The reaction material was stirred at room temperature for 5 hours and further heated at 80C for 16 hours. The reaction material was then cooled to 0C and extracted with ethyl acetate (4 x 150 mL). The organic layer was washed with brine solution, dried over Na2SO4 and concentrated. The crude material was purified by silica gel column elution with hexane:EtOAc to yield Intermediate-33 (5.5 g) as a brown solid.
