反应详情

In a 3 L reactor, set for reflux under positive nitrogen pressure and using a bleach scrubber, was prepared a solution of potassium cyanide (68.32 g, 1.04M) in EtOH (136 mL) and water (255 mL). The mixture was heated to reflux, at which point a solution of 2-chloro-3-(chloromethyl)pyridine (Intermediate 1; 170.0 g, 1.04M) in EtOH (170 mL) was added dropwise over 30 minutes. The whole mixture was maintained at reflux for a further 150 minutes. The mixture was then allowed to cool just below boiling point and the equipment set for distillation. A total of 8.5 volumes of EtOH were removed. On cooling, half a volume of water was added. At a temperature of 40° C., the solution was seeded and crystallised instantaneously. The thick beige slurry was allowed to cool to ambient temperature and then to 0° C. This mixture was filtered, rinsed with cold water (2 vols) and dried at 45° C. in a vacuum oven overnight. The title compound was afforded as a beige solid in excellent yield and purity (126.9 g, 80%). δH (d6-DMSO, 300 MHz) 8.45 (1H, dd), 8.00 (1H, dd), 7.50 (1H, dd), 4.15 (2H, s). LCMS (ES)+ RT 2.15 min, m/e 153.01 & 155.01 (M+1 & M+3, Product).

1. customIn a 3 L reactor, set
2. temperaturefor reflux under positive nitrogen pressure
3. temperatureThe mixture was heated
4. additionwas added dropwise over 30 minutes
5. temperatureThe whole mixture was maintained
6. temperatureat reflux for a further 150 minutes
7. temperatureto cool just
8. distillationthe equipment set for distillation
9. customA total of 8.5 volumes of EtOH were removed
10. temperatureOn cooling
11. additionhalf a volume of water was added
12. customAt a temperature of 40° C.
13. customcrystallised instantaneously
14. customto 0° C
15. filtrationThis mixture was filtered
16. washrinsed with cold water (2 vols)
17. customdried at 45° C. in a vacuum oven overnight