反应详情

A solution of 3-[2-(3-chlorophenyl)ethyl]-N-(1,1-dimethylethyl)-2-pyridine carboxamide (175 g, 0.554 mole), in 525 mL (863 g, 5.63 mole) of phosphorous oxychloride is heated at reflux for 3 hours. Completion of the reaction is determined by thin layer chromatography. Excess phosphorous oxychloride is removed by distillation at reduced pressure and the residue is quenched into a mixture of water and isopropanol. The pH is brought to 5-7 by addition of 50% aqueous sodium hydroxide solution while maintaining the temperature below 30° C. The crystalline slurry of crude product is filtered and washed with water. Crude product is purified by slurrying the wet cake in hot isopropanol followed by cooling at 0°-5° C. The product is filtered, washed with hexane and dried at below 50° C. Yield: 118 g (HPLC purity 95.7%), m.p. 72°-73° C., 89.4% of theory.

1. temperatureat reflux for 3 hours
2. customExcess phosphorous oxychloride is removed by distillation at reduced pressure
3. customthe residue is quenched into a mixture of water and isopropanol
4. additionThe pH is brought to 5-7 by addition of 50% aqueous sodium hydroxide solution
5. temperaturewhile maintaining the temperature below 30° C
6. filtrationThe crystalline slurry of crude product is filtered
7. washwashed with water
8. customCrude product is purified
9. temperatureby cooling at 0°-5° C
10. filtrationThe product is filtered
11. washwashed with hexane
12. customdried at below 50° C