反应详情

温度

45 °C

1-(6-methoxy-naphthalen-2-yl)heptan-1-one (0.176 kg, 0.651 moles) was dissolved in anhydrous ethanol (1.56 L), 1-benzyl-1-phenylhydrazine hydrochloride (BPH, 0.168 kg, 0.716 moles) was added, a 37% aqueous solution of hydrochloric acid (1.2 g, 12.2 mmoles) was added, and the reaction mixture was heated under reflux for 7 hours. Two portions of BPH (8.4 g, 71.6 mmoles each) were added to the mixture at one hour intervals at 70° C. The temperature of the mixture returned to the reflux temperature after the first BPH addition. Heating was terminated, the reaction mixture was diluted with heptane (1.65 L) followed by water (0.62 kg), and the mixture was stirred for 30 minutes while maintaining the temperature at 45° C. The addition of heptane resulted in the precipitation of solids from the homogeneous organic phase, while the addition of water brought the mixture to a biphasic state with layers in an approximate ratio of 1:1. The bottom layer was drained (pH 1) and the upper layer was washed with water (0.26 kg) while stirring the mixture for 30 minutes. The bottom layer was again drained (pH 3) and the upper layer was cooled to 12° C. in the reactor. All operations subsequent to the quenching step were conducted at 45° C. to prevent premature product crystallization. About 10 grams of the chilled solution were withdrawn from the reactor, subjected to low-temperature crystallization, and returned to the chilled solution as a seeding suspension. The mixture was kept at 12° C. for 30 minutes, cooled to −10° C. over two hours, and stirred at that temperature for 30 minutes. The suspension was filtered, the solids were dried in a nitrogen stream on a filter for 30 minutes, and the solids were vacuumed at 50° C./50 mm Hg to yield 221 g (78%) of the title compound as light-yellow prills with 99.45% ar. HPLC purity.

1. temperaturethe reaction mixture was heated
2. temperatureunder reflux for 7 hours
3. temperatureHeating
4. customwas terminated
5. additionthe reaction mixture was diluted with heptane (1.65 L)
6. additionThe addition of heptane
7. customresulted in the precipitation of solids from the homogeneous organic phase, while the addition of water
8. washthe upper layer was washed with water (0.26 kg)
9. stirringwhile stirring the mixture for 30 minutes
10. temperaturethe upper layer was cooled to 12° C. in the reactor
11. customwere conducted at 45° C.
12. customproduct crystallization
13. customAbout 10 grams of the chilled solution were withdrawn from the reactor
14. customsubjected to low-temperature crystallization
15. waitThe mixture was kept at 12° C. for 30 minutes
16. temperaturecooled to −10° C. over two hours
17. stirringstirred at that temperature for 30 minutes
18. filtrationThe suspension was filtered
19. customthe solids were dried in a nitrogen stream on
20. filtrationa filter for 30 minutes
21. customwere vacuumed at 50° C.