反应详情

温度

80 °C

1-Bromo-5-chloropentane (84.7 g, 60.2 mL) is added to a stirred slurry of 4-hydroxy-3-methoxy-N,N-bis(1-methylethyl)benzamide (109 g) and powdered potassium carbonate (72.1 g) in 2-butanone (805 g, 1099 mL). The reaction mixture is heated at 80° C. for 21 hours with moderate stirring, and the slurry is filtered hot to obtain a 2-butanone solution containing 4-(5-chloropentyloxy)-3-methoxy-N,N-bis(1-methylethyl)benzamide. Sodium iodide (97.8 g) is added. The mixture is heated at 80° C. for 21 hours with moderate stirring, and filtered while hot to obtain a 2-butanone solution of 4-(5-iodopentyloxy-3-methoxy-N,N-bis(1-methylethyl)benzamide. Powdered potassium carbonate (72.1 g) and 4-cyanophenol (67.4 g) are added. After the mixture is stirred moderately for 5 minutes, tris[2-(2-methoxyethoxy)ethyl]amine (3.52 g) is added in one portion and the resulting slurry is heated at 78°-80° C. for 21 hours with moderate stirring. The slurry is cooled to 25°-35° C. and sodium hydroxide (1N, 500 mL) is added. The mixture is stirred for 10 minutes, and the aqueous layer is then separated. The organic layer (ca. 1300 mL) is washed with saturated sodium chloride solution (500 mL), and 940 mL of the solvent is removed by distillation at 115° C. The remaining solution is cooled to 60° C., cyclohexane (1526 mL) is added over a 5 minute period, followed by antistatic agent (ASA-3, 0.17 g). The mixture is heated at 76°-79° C. for 5 minutes and filtered hot under vacuum. The filtrate is heated at 76°-79° C. for 5 minutes, cooled slowly to room temperature and stirred over the weekend. The suspension is then cooled to -8°-12° C. and stirred at this temperature for 1.5 hours. The slurry is filtered, the collected product is washed with 2-butanone (22.2 mL)/cyclohexane (178 mL), and dried at 46°-50° C. for 24 hours to yield 4-[5-(4-cyanophenoxy)pentyloxy-3-methoxy-N,N-bis(1-methylethyl)benzamide. Crude product (144 g) is purified by suspending in 2-butanone (215 mL)/cyclohexane (1218 mL) with antistatic agent, heating at about 80° for 5 minutes, faltering the solution while hot, cooling the filtrate to room temperature, stirring overnight, then cooling to 8°-10° C. and stirring for 1.5 hours at 8°-10° C. The slurry is vacuum filtered, the collected product is washed with 2-butanone/cyclohexane, and dried at 46°-50° in a vacuum oven for 24 hours to obtain pure 4-[5-(4-cyanophenoxy)pentyloxy]-3-methoxy-N,N-bis(1-methylethyl)benzamide; 1H-NMR (DMSO): δ1.10-1.50 (m, 12H), 1.50-1.65 (m, 2H), 1.75-1.85 (m, 4H), 3.55-3.80 (m, 2H), 3.75 (s, 3H), 3.96 (t, J=6.3 Hz, 2H) 2H), 6.75-6.85 (m, 2H), 6.92-6.98 (d, J=8.7 Hz, 1H), 7.06-7.12 (d, J=8.5 Hz, 2H), 7.72-7.78 (d, J=8.4 Hz, 2H).

1. filtrationthe slurry is filtered hot
2. customto obtain a 2-butanone solution
3. temperatureThe mixture is heated at 80° C. for 21 hours with moderate stirring
4. filtrationfiltered while hot