Ammonia → 1-Azabicyclo[2.2.2]octane-4-carbonitrile

Quinuclidin-4-ylcarbonylchloride hydrochloride (Example 8, Step 4) (3.4 g 0.0016 moles) was dissolved in acetonitrile (150 ml) and treated with 35% ammonia solution (50 ml). The mixture was stirred for 18 hours at ambient temperature then concentrated to dryness in vacuo. 1 g of the residue was then treated with phosphoms oxychloride (8 ml) at reflux for 5 hours. The mixture was then concentrated in vacuo and the residue partitioned between saturated potassium carbonate and diethylether (4×50 ml). The combined organic extracts were dried (Na2SO4), filtered and concentrated. Column chromatography on silica gel elutin with 0-5% methanol/chloroform gave the title compound 0.34 g (75%); 1H NMR (CDCl3) 1.85 (6H t, J 10 Hz), 2.91 (6H, t, J 10 Hz).

1. concentrationthen concentrated to dryness in vacuo
2. addition1 g of the residue was then treated with phosphoms oxychloride (8 ml)
3. temperatureat reflux for 5 hours
4. concentrationThe mixture was then concentrated in vacuo
5. customthe residue partitioned between saturated potassium carbonate and diethylether (4×50 ml)
6. dry with materialThe combined organic extracts were dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated

ORD record

ord-5d0d6269356c41cba39bfbfe0d290e8e

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

USRE043390E1