反应详情

温度

2.5 °C

Diaminodipropyluracil hydrochloride (VI, 1.36 wt) is suspended in acetonitrile (12.5 vol), cooled to 0 to 5° C. and triethylamine (2.46 vol) is added between 0 to 10° C. The mixture is then cooled to 0 to 5° C. A mixture of 4-chlorocarbonylbicyclo[2.2.2]-octane-1-carboxylic acid methyl ester (V, Example 82) in acetonitile is added to the diaminodipropyluracil mixture between 0 to 20° C. The reaction mixture is then warmed to 15 to 25° C. and stirred for 15 to 20 hours by which time all of the 4-chlorocarbonylbicyclo[2.2.2]octane-1-carboxylic acid methyl ester (V) is consumed (TLC; dichloromethane/methanol, 9/1; visualization Bromocresol green). The reaction mixture is diluted with water (3.12 vol) and concentrated under reduced pressure at 40 to 45° C. (18 to 20 vol of solvent is removed). The concentrate is extracted with ethyl acetate (3×6 vol) and the combined organics are washed sequentially with citric acid (10%, 3×3.12 vol), hydrochloric acid (1M, 2.5 vol), water (3.12 vol), saturated sodium bicarbonate (3.12 vol) and saline (3.12 vol). The mixture is dried over magnesium sulphate (0.75 wt) for 5 to 15 min, filtered, washed with ethyl acetate (1 vol) and the solvent removed under reduced pressure at 40 to 45° C. to give the title compound.

1. temperatureThe mixture is then cooled to 0 to 5° C
2. temperatureThe reaction mixture is then warmed to 15 to 25° C.
3. customis consumed (TLC; dichloromethane/methanol, 9/1; visualization Bromocresol green)
4. additionThe reaction mixture is diluted with water (3.12 vol)
5. concentrationconcentrated under reduced pressure at 40 to 45° C.
6. custom(18 to 20 vol of solvent is removed)
7. extractionThe concentrate is extracted with ethyl acetate (3×6 vol)
8. washthe combined organics are washed sequentially with citric acid (10%, 3×3.12 vol), hydrochloric acid (1M, 2.5 vol), water (3.12 vol), saturated sodium bicarbonate (3.12 vol) and saline (3.12 vol)
9. dry with materialThe mixture is dried over magnesium sulphate (0.75 wt) for 5 to 15 min
10. filtrationfiltered
11. washwashed with ethyl acetate (1 vol)
12. customthe solvent removed under reduced pressure at 40 to 45° C.