反应详情

A 500-mL four-necked flask equipped with a mechanical stirrer, thermocouple, condenser and sodium hydroxide/sodium hypochlorite scrubber was charged with 2-amino-5-bromo-N,3-dimethylbenzamide (prepared by the method of Example 1) (99.1% purity, 24.1 g, 0.10 mol) and xylenes (100 g) while maintaining an atmosphere of argon through a gas inlet line connected to the condenser. The mixture was stirred at room temperature, and powdered sodium cyanide (powdered just prior to use) (6.2 g, 0.121 mol, assuming 95% purity), copper(I) iodide (2.9 g, 0.015 mol) and N,N′-dimethylethylenediamine (7.6 g, 0.085 mol) were added. Stirring was continued for an additional 15 to 20 minutes while the mixture was purged with argon, after which time the mixture was maintained under an argon atmosphere. The mixture was heated at reflux (about 140° C.), while venting through the scrubber. After 4.5 h the mixture was cooled to 25° C., water (100 mL) was added over 5 minutes, and stirring was continued for an additional 30 minutes. The mixture was filtered and the solid collected was washed with water (2×50 mL) and xylenes (50 mL), and then dried to a constant weight in a vacuum-oven at 55° C. to give the title compound (18.2 g) as an off-white solid melting at 203-204° C.

1. customA 500-mL four-necked flask equipped with a mechanical stirrer
2. temperaturewhile maintaining an atmosphere of argon through a gas inlet line
3. stirringStirring
4. customwas purged with argon
5. temperatureafter which time the mixture was maintained under an argon atmosphere
6. temperatureThe mixture was heated
7. temperatureat reflux (about 140° C.)
8. temperatureAfter 4.5 h the mixture was cooled to 25° C.
9. additionwater (100 mL) was added over 5 minutes
10. stirringstirring
11. waitwas continued for an additional 30 minutes
12. filtrationThe mixture was filtered
13. customthe solid collected
14. washwas washed with water (2×50 mL) and xylenes (50 mL)
15. customdried to a constant weight in a vacuum-oven at 55° C.