反应详情

温度

56 °C

A 4-neck 12 L flask equipped with a mechanical stirrer, thermocouple, nitrogen inlet, and gas adapter connected to a bubbler was charged with 3-(3-bromophenyl)-4-(4-chlorophenyl)butan-2-one, zinc cyanide (201 g), and dimethylformamide 4.0 L. Nitrogen gas was bubbled through the suspension for 30 min at room temperature and for 1 h at 56° C. using a heating mantle. The bromoketone/Zn(CN)2 slurry (at 56° C.) was added to the catalyst solution (at 56° C.). After the transfer was complete, the reaction mixture was stirred at 56° C. for 4.5 h under N2. The resulting suspension was cooled in an ice bath, and 30% aqueous ammonium hydroxide (971 mL) was added over 5 min, keeping the temperature below 30° C. The suspension was warmed to room temperature, stirred for 60 min, and then filtered through a pad of SOLKA FLOC eluting with toluene (5 L). The filtrate was added into an extractor containing 20% aqueous ammonium hydroxide (6.9 L) and 5 L of toluene. The biphasic mixture was stirred at room temperature for 15 min and then separated. The organic layer was washed with 7 L of brine (1:1 saturated NaCl:Water), then 7 L of water. The organic phase was transferred to a 12 L 4 neck flask equipped with an overhead stirrer, thermocouple, mechanical stirrer, and connected to a batch concentrator. The batch was concentrated under vacuum at 15-38° C. to a volume of 1.5 L, and then heptane (850 mL) was added.

1. customA 4-neck 12 L flask equipped with a mechanical stirrer
2. customthermocouple, nitrogen inlet, and gas adapter connected to a bubbler
3. customNitrogen gas was bubbled through the suspension for 30 min at room temperature and for 1 h at 56° C.
4. additionThe bromoketone/Zn(CN)2 slurry (at 56° C.) was added to the catalyst solution (at 56° C.)
5. temperatureThe resulting suspension was cooled in an ice bath
6. addition30% aqueous ammonium hydroxide (971 mL) was added over 5 min
7. customthe temperature below 30° C
8. temperatureThe suspension was warmed to room temperature
9. stirringstirred for 60 min
10. filtrationfiltered through a pad of SOLKA FLOC
11. washeluting with toluene (5 L)
12. additionThe filtrate was added into an extractor
13. additioncontaining 20% aqueous ammonium hydroxide (6.9 L) and 5 L of toluene
14. stirringThe biphasic mixture was stirred at room temperature for 15 min
15. customseparated
16. washThe organic layer was washed with 7 L of brine (1:1 saturated NaCl:Water)
17. customequipped with an overhead stirrer
18. customthermocouple, mechanical stirrer, and connected to a batch concentrator
19. concentrationThe batch was concentrated under vacuum at 15-38° C. to a volume of 1.5 L
20. additionheptane (850 mL) was added