反应详情

Two hundred L of THF was added to a reactor, and 24.6 kg of (4aR)-(10bR)-8-chloro-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one was added. Then 35 kg of methyl iodide was added, rinsed in with 10 L of THF. A 79.6 kg portion of 50% aqueous sodium hydroxide was added in 13 minutes at 15°-25°, rinsed in with 40 L of THF. The mixture was stirred at 36°-39° for 13 hours, and was then cooled to 15°-25°. The layers were allowed to separate, and the water/THF phase was neutralized to pH 7 with hydrochloric acid and heated to reflux. Distillate was removed until the temperature reached 77°. A total of 154 kg of water was added from time to time. The solution was cooled over 3 hours to 3°-10°, and was then stirred vigorously at that temperature until solids began to form. Then the slurry was stirred gently at constant temperature for 3 hours. The slurry was filtered, and the vessel and filter cake were washed with cold water. The cake was air dried at 25°-35° for 75 hours to obtain 27.3 kg of the desired product, potency 85.1% by liquid chromatographic analysis.

1. washrinsed in with 10 L of THF
2. additionA 79.6 kg portion of 50% aqueous sodium hydroxide was added in 13 minutes at 15°-25°
3. washrinsed in with 40 L of THF
4. temperaturewas then cooled to 15°-25°
5. customto separate
6. temperatureheated to reflux
7. customDistillate was removed until the temperature
8. customreached 77°
9. additionA total of 154 kg of water was added from time to time
10. temperatureThe solution was cooled over 3 hours to 3°-10°
11. stirringwas then stirred vigorously at that temperature until solids
12. customto form
13. stirringThen the slurry was stirred gently at constant temperature for 3 hours
14. filtrationThe slurry was filtered
15. filtrationthe vessel and filter cake
16. washwere washed with cold water
17. customdried at 25°-35° for 75 hours