反应详情

Powdered potassium hydroxide (96.7 g) is added to a suspension of 2-cyanophenothiazine (242 g) in methyl ethyl ketone (2.2 liters). The temperature of the mixture rises spontaneously to 24° C. and the mixture is brought to 60° C. for half an hour while stirring. The toluene solution of 2-chloro-1-dimethylaminopropane prepared above is added in the course of 30 minutes. The mixture is heated under reflux for 12 hours. After cooling, the mixture is transferred to a separating funnel and washed with distilled water (2×2 liters). The organic phase is dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C. to give an oil, which is diluted in ethyl ether (2 liters). The solution obtained is cooled and primed by scratching. The crystallized yellow precipitate is removed by filtration. The mother liquors are concentrated to dryness under reduced pressure (100 mm Hg; 13.3 kPa) at 30° C. to give a brown oil which is purified by chromatography on a column (height: 80 cm; diameter: 8.5 cm) of silica (0.2-0.06 mm), eluting with an 80:20 (by volume) mixture of cyclohexane and ethyl acetate and collecting 1-liter fractions. Fractions 7 to 16 are combined and concentrated to dryness at 50° C. under reduced pressure (30 mm Hg; 4 kPa) to give 10-[(2RS)-1-dimethylamino-2-propyl]-2-phenothiazinecarbonitrile (54.8 g) in the form of a brown oil.

1. customrises spontaneously to 24° C.
2. waitthe mixture is brought to 60° C. for half an hour
3. additionabove is added in the course of 30 minutes
4. temperatureThe mixture is heated
5. temperatureunder reflux for 12 hours
6. temperatureAfter cooling
7. customthe mixture is transferred to a separating funnel
8. washwashed with distilled water (2×2 liters)
9. dry with materialThe organic phase is dried over magnesium sulphate
10. filtrationfiltered
11. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C.
12. customto give an oil, which
13. customThe solution obtained
14. temperatureis cooled
15. customThe crystallized yellow precipitate is removed by filtration
16. concentrationThe mother liquors are concentrated to dryness under reduced pressure (100 mm Hg; 13.3 kPa) at 30° C.
17. customto give a brown oil which
18. customis purified by chromatography on a column (height: 80 cm; diameter: 8.5 cm) of silica (0.2-0.06 mm)
19. washeluting with an 80:20 (by volume) mixture of cyclohexane and ethyl acetate
20. customcollecting 1-liter fractions
21. concentrationconcentrated to dryness at 50° C. under reduced pressure (30 mm Hg; 4 kPa)