Water → 2,3,4,4a,9,9a-Hexahydro-1H-indeno(2,1-b)pyridine-6-carbonitrile

HRID 873036Notes

Reaction equation

[NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]2[C:7]3[CH:8]=[C:9]([C:14]([NH2:16])=O)[CH:10]=[CH:11][C:12]=3[CH2:13][CH:2]12.O=P(Cl)(Cl)Cl.O>O1CCOCC1>[NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]2[C:7]3[CH:8]=[C:9]([C:14]#[N:16])[CH:10]=[CH:11][C:12]=3[CH2:13][CH:2]12

Participants

Conditions

Temperature: 25 °C

Procedure

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%.

Workup

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

Sources & evidence

ORD record: ord-1b41c2ba8bb84b9dbf2da3f7aaeef945
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08975405B2

Reaction notes

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