反应详情

温度

0 °C

A 3-neck 12 L flask equipped with an overhead stirrer, thermometer, condenser and nitrogen inlet was charged with NaH (186.1 g, 4.653 mol) and DMF (1500 mL). The slurry was cooled to 0° C. and a solution of 4-iodophenol (488.6 g, 2.221 mol) in DMF (1500 mL) and added. The temperature of the reaction mixture was maintained below 25-30° C. during this addition. After complete addition, the cooling bath was promptly removed and the mixture continued to stir at RT for 1 h. 5-Bromo-2-chloronicotinic acid (500 g, 2.115 mol) was then added to the slurry portion wise. The reaction mixture was heated to 115° C. overnight. The dark brown reaction mixture was cooled to 20° C. and diluted with water (2 L). The reaction mixture was acidified using HOAc (845 ml). The black homogenous solution (pH=5) was allowed to stir for 1 h at RT and poured slowly onto ice-water (20 L). The slurry was filtered at RT, washed with water (2×2 L) and dried in air to give 765 g of 5-Bromo-2-(4-iodophenoxy)-nicotinic acid as light orange solid.

1. customA 3-neck 12 L flask equipped with an overhead stirrer
2. temperatureThe temperature of the reaction mixture was maintained below 25-30° C. during this addition
3. additionAfter complete addition
4. customthe cooling bath was promptly removed
5. temperatureThe reaction mixture was heated to 115° C. overnight
6. temperatureThe dark brown reaction mixture was cooled to 20° C.
7. stirringto stir for 1 h at RT
8. additionpoured slowly onto ice-water (20 L)
9. filtrationThe slurry was filtered at RT
10. washwashed with water (2×2 L)
11. customdried in air