反应详情

温度

-78 °C

Hexahydro-7-(2-propenyl)-1H-azepin-2-imine, monohydrochloride (the product of EXAMPLE 108) (3.0 g, 14.7 mmol) is dissolved in a mixture of methylene chloride (100 mL) and methanol (50 mL) and cooled to -78° C. Ozone is then bubbled through until a blue color is observed. The reaction is flushed with N2 to remove excess ozone. The reaction mixture is warmed to room temperature and concentrated in vacuo to a residue. The residue is dissolved in ethanol (100 mL), cooled to 0° C., and vigorously stirred as a cold solution of sodium borohydride (0.7 g, 18.5 mmol) in 1:1 ethanol-water is added. The pH of the reaction mixture is maintained by the concomitant addition of 2M acetic acid in water, maintaining the pH (pH paper) at 8 to 9. After the addition is complete, the mixture is stirred at room temperature for 10 hr, the reaction mixture is acidified to pH 2 with dilute HCl, and the reaction mixture is concentrated in vacuo to a gum. The gum is dissolved in a small amount of ethanol, filtered, evaporated in vacuo to a solid, dissolved in water and applied to an ion exchange column of Dowex 50 (H+). The column is washed with deionized water, and the title compound eluted with 2N HCl. The eluate is concentrated in vacuo to a solid, dissolved in a small amount of water, filtered, and lyophilized to give the title compound. C8H16N2O.HCl mw=192.69

1. customOzone is then bubbled through until a blue color
2. customThe reaction is flushed with N2
3. customto remove excess ozone
4. temperatureThe reaction mixture is warmed to room temperature
5. concentrationconcentrated in vacuo to a residue
6. dissolutionThe residue is dissolved in ethanol (100 mL)
7. temperaturecooled to 0° C.
8. additionis added
9. temperaturemaintaining the pH (pH paper) at 8 to 9
10. additionAfter the addition
11. concentrationthe reaction mixture is concentrated in vacuo to a gum
12. dissolutionThe gum is dissolved in a small amount of ethanol
13. filtrationfiltered
14. customevaporated in vacuo to a solid
15. dissolutiondissolved in water
16. washThe column is washed with deionized water
17. washthe title compound eluted with 2N HCl
18. concentrationThe eluate is concentrated in vacuo to a solid
19. dissolutiondissolved in a small amount of water
20. filtrationfiltered