198474-05-4

541-59-3

399-52-0

198474-05-4

The general procedure for the synthesis of 3-(5-fluoro-1H-indol-3-yl)-2,5-pyrrolidinedione from maleimide and 5-fluoroindole was as follows: 5-fluoroindole (5.00 g, 35.5 mmol, 96 wt%) was mixed with maleimide (5.17 g, 53.3 mmol, 1.5 eq.) in a 50 mL reaction vessel followed by addition of acetonitrile ( 15.0 mL, 11.7 g, 286 mmol, 100 wt%) and zinc chloride (5.08 g, 37.3 mmol, 1.05 equiv). The reaction mixture was heated to 85 °C within 10 min and maintained at this temperature for 24 h. The reaction was carried out at a temperature of 0.5 °C. The reaction was carried out at a temperature of 0.5 °C. During the reaction, the temperature was maintained above 80 °C and water (30.0 mL, 30.0 g, 1670 mmol, 100 wt%) was slowly added and yellow solid precipitation was observed. Subsequently, the reaction mixture was cooled to 50 °C over 1 h and stirred at this temperature for 2 h, after which it continued to be cooled to 10 °C over 1 h and stirred at 10 °C for 1 h. The reaction mixture was then cooled to 50 °C over 1 h and stirred at 10 °C for 2 h. The reaction mixture was then The solid was collected by filtration and the filter cake was washed twice with 5 mL of a 1:1 acetonitrile/water mixture to give the crude product (6.85 g, 29.5 mmol, 83.1% yield). To purify the crude product, it (6.85 g, 29.5 mmol, 100 wt%) was dissolved in tetrahydrofuran (41.1 mL, 36.4 g, 505 mmol, 100 wt%) and heated to 66 °C to form a homogeneous solution. Heptane (27.4 mL, 18.7 g, 187 mmol, 100 wt%) was slowly added at 66 °C and the solid was observed to start precipitating. The mixture was cooled to 25 °C over 3 h, filtered and washed with heptane, followed by drying in a high vacuum oven overnight to give the purified product (4.93 g, 21.2 mmol, 100 wt%, 72.0% yield). For further purification, the above product (1.00 g, 4.3 mmol, 100 wt%) was mixed with tetrahydrofuran (6 mL, 100 wt%) and heptane (6 mL, 100 wt%) in a 50 mL vessel and stirred for 48 h at 25 °C. The product was purified by washing with a solvent and dried in a high vacuum oven overnight. The solid was collected by filtration and dried in a high vacuum oven overnight to give the final product (0.89 g, 3.83 mmol, 100 wt%, 89.00% yield).