反应详情

温度

25 °C

A mixture of 2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridine-6-carboxamide (I), hydrogen chloride salt (7.5 Kg, 25.2 mol) and dioxane (15 L) is stirred for 30 minutes at 25° C. and treated with POCl3 (7.77 Kg, 50.4 mol). The mixture is heated to 80° C. over 1 hour and held at 80° C. for 2 hours. The mixture is cooled to 20-25° C., treated over about 30 minutes with a solution of water (1.376 L, 75.6 mol) in dioxane (30 L), stirred for 30 minutes, and treated with additional water (1.376 L, 75.6 mol). The resulting slurry is stirred at 25° C. for about 18 hours and filtered. The resulting filter cake is washed portion-wise with 3.0 L of 1% H2O in 1,4-dioxane and dried for about 18 hours at ˜50° C. to provide 2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridine-6-carbonitrile (III) in the form of the hydrogen chloride salt. Yield: 4.73 Kg, 20.16 mol; 80%.

1. temperatureThe mixture is heated to 80° C. over 1 hour
2. waitheld at 80° C. for 2 hours
3. temperatureThe mixture is cooled to 20-25° C.
4. stirringstirred for 30 minutes
5. stirringThe resulting slurry is stirred at 25° C. for about 18 hours
6. filtrationfiltered
7. filtrationThe resulting filter cake
8. washis washed portion-wise with 3.0 L of 1% H2O in 1,4-dioxane
9. customdried for about 18 hours at ˜50° C.