反应详情

A solution of (2RS)-2-(2-cyano-10-phenothiazinyl)-1-propyl methanesulphonate (14.4 g) and (3RS)-3-methylpiperidine (9.4 cc) in toluene (75 cc) is stirred under reflux for 20 hours. After cooling, the mixture is extracted with N aqueous hydrochloric acid solution (2×100 cc). The combined aqueous phases are alkalinized with caustic soda (d=1.33) to pH 13 and extracted with ethyl acetate (2×200 cc). The combined organic phases are washed successively with distilled water (2×50 cc) and with saturated aqueous sodium chloride solution (50 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residual yellow oil (14.4 g) is purified by chromatography on a column (height: 40 cm; diameter: 4 cm) of silica gel (0.2-0.063 mm), eluting with a mixture (80:20 by volume) (2.5 liters) of cyclohexane and ethyl acetate and collecting 100-cc fractions. The combined fractions 10 to 12 are concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. 10-((2RS)-1-[(3RS)-3-Methyl-1-piperidyl]-2-propyl}-2-phenothiazinecarbonitrile (7.2 g) is thereby obtained in the form of a yellow oil, which is subsequently used as it is.

1. temperatureunder reflux for 20 hours
2. temperatureAfter cooling
3. extractionthe mixture is extracted with N aqueous hydrochloric acid solution (2×100 cc)
4. extractionextracted with ethyl acetate (2×200 cc)
5. washThe combined organic phases are washed successively with distilled water (2×50 cc) and with saturated aqueous sodium chloride solution (50 cc)
6. dry with materialdried over magnesium sulphate
7. filtrationfiltered
8. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
9. customThe residual yellow oil (14.4 g) is purified by chromatography on a column (height: 40 cm; diameter: 4 cm) of silica gel (0.2-0.063 mm)
10. washeluting with a mixture (80:20 by volume) (2.5 liters) of cyclohexane and ethyl acetate
11. customcollecting 100-cc fractions
12. concentrationThe combined fractions 10 to 12 are concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C