反应详情

温度

30 °C

Step DI: Suspend ethyl 3-(4-bromophenyl)-4-cyano-5-ethylpyrrole-2-carboxylate (7.0 kg, 20.17 mol, 1 eq, prepared in step C above) in acetone (70 L) in a 100-L reactor. Add water (0.7 L), iodomethane (3.153 kg, 1.38 L, 22.21 mol, 1.1 eq), and potassium carbonate (5.58 kg, 40.37 mol, 2 eq). Stir the mixture at 30° C. for 14 h. Concentrate the reaction mixture by removing 41 L of solvent by distillation at 50° C. under reduced pressure. Add water (55 L) slowly over 45 min at 20-22° C. Cool the suspension to 0° C. within 1 h and stir for an additional h at this temperature. Collect the precipitate by filtration and wash with a cold (0-5° C.) mixture of acetone/water (1.2+3 L.) and then with water (4.2 L). Dry the product in 100-L rotary evaporator under reduced pressure at 60° C. for 66 h to obtain 7.133 kg of title compound as a beige powder (98% yield). 1H NMR (CDCl3, 500.0 MHz): δ 1.08 (t, J=7.1 Hz, 3H), 1.34 (t, J=7.1 Hz, 3H), 2.88 (q, J 2 0=7.1 Hz, 2H), 3.92 (s, 3H), 4.13 (q, J=7.1 Hz, 2H), 7.26 (d, J=8.8 Hz, 2H), 7.54 (d, J=8.8 Hz, 2H); 13C NMR DMSO-d6, 125.7 MHz): δ 12.96, 13.44, 18.79, 60.16, 92.04, 115.22, 119.96, 121.12, 130.73, 131.58, 131.86, 132.05, 147.87, 159.82; Anal. Calcd for C17H17BrN2O2: C, 56.52; H, 4.74; Br, 22.12; N, 7.75; 0, 8.86. Found: C, 56.32; H, 4.72; N, 7.73; IR (KBr): 3347, 2979, 2938, 2216, 1698, 1441, 1510, 1476, 1400, 1379, 1258, 1212, 1110, 771 cm−1.

1. concentrationConcentrate the reaction mixture
2. customby removing 41 L of solvent
3. distillationby distillation at 50° C. under reduced pressure
4. waitAdd water (55 L) slowly over 45 min at 20-22° C
5. temperatureCool the suspension to 0° C. within 1 h
6. stirringstir for an additional h at this temperature
7. customCollect the precipitate
8. filtrationby filtration
9. washwash with a cold (0-5° C.) mixture of acetone/water (1.2+3 L.)
10. customDry the product
11. customin 100-L rotary evaporator under reduced pressure at 60° C. for 66 h