反应详情

温度

20 °C

Into a suspension of sodium borohydride (52 g) in tetrahydrofuran (1.4 liters), 1,2-ethanedithiol (113 cc) is introduced with stirring in the course of 15 minutes and at a temperature in the region of 20° C., followed, in the course of 15 minutes under the same conditions, by a solution of ethyl (2RS)-2-(2-cyano-10-phenothiazinyl)propionate (296 g) in tetrahydrofuran (1.4 liters). When the addition is complete, the reaction mixture is heated for 20 hours to a temperature in the region of 60° C. After cooling to a temperature of 5° C., 4N aqueous sodium hydroxide solution (1 liter) is introduced during 1 hour: a brisk evolution of gas is observed. The reaction mixture is then poured into a mixture of 4N aqueous sodium hydroxide solution (1 liter) and methylene chloride (3 liters) with stirring. The organic phase is isolated and the aqueous phase re-extracted with methylene chloride (1 liter). The combined organic phases are washed with saturated aqueous sodium chloride solution (2×1 liter), dried over magnesium sulphate, filtered and concentrated t dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. The viscous orange oil (290 g) is purified on a column (height: 50 cm; diameter: 8.5 cm) of silica gel (0.2-0.063 mm), eluting successively with methylene chloride (3 liters), then with a mixture (97.5:2.5 by volume) (4 liters) of methylene chloride and methanol and with a mixture (95:5 by volume) (10 liters) of methylene chloride and methanol and collecting 1-liter fractions. Fractions 3 to 15 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. 10-[(2RS)-1-Hydroxy-2-propyl]-2-phenothiazinecarbonitrile (169.7 g) is thereby obtained in the form of a yellow solid, m.p. 123° C.

1. additionis introduced
2. additionWhen the addition
3. temperaturethe reaction mixture is heated for 20 hours to a temperature in the region of 60° C
4. additionis introduced during 1 hour
5. stirringwith stirring
6. customThe organic phase is isolated
7. extractionthe aqueous phase re-extracted with methylene chloride (1 liter)
8. washThe combined organic phases are washed with saturated aqueous sodium chloride solution (2×1 liter)
9. dry with materialdried over magnesium sulphate
10. filtrationfiltered
11. concentrationconcentrated t dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C
12. customThe viscous orange oil (290 g) is purified on a column (height: 50 cm; diameter: 8.5 cm) of silica gel (0.2-0.063 mm)
13. washeluting successively with methylene chloride (3 liters)
14. customwith a mixture (97.5:2.5 by volume) (4 liters) of methylene chloride and methanol and with a mixture (95:5 by volume) (10 liters) of methylene chloride and methanol and collecting 1-liter fractions
15. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C