Diethyl Ether → 2-(Pyridin-3-ylmethyl)quinuclidin-3-amine

To a stirred solution of 2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octan-3-one (3.00 g, 13.9 mmol) in dry methanol (20 mL), under nitrogen, was added a 1 M solution of ZnCl2 in ether (2.78 mL, 2.78 mmol). After stirring at ambient temperature for 30 min, this mixture was treated with solid ammonium formate (10.4 g, 167 mmol). After stirring another hour at ambient temperature, solid sodium cyanoborohydride (1.75 g, 27.8 mmol) was added in portions. The reaction was then stirred at ambient temperature overnight and terminated by addition of water (˜5 mL). The quenched reaction was partitioned between 5 M NaOH (10 mL) and chloroform (20 mL). The aqueous layer was extracted with chloroform (20 mL), and combined organic layers were dried (Na2SO4), filtered and concentrated. This left 2.97 g of yellow gum. GC/MS analysis indicated that the product was a 90:10 mixture of the cis and trans amines, along with a trace of the corresponding alcohol (98% mass recovery).

1. stirringAfter stirring another hour at ambient temperature
2. stirringThe reaction was then stirred at ambient temperature overnight
3. customterminated by addition of water (˜5 mL)
4. customThe quenched reaction
5. customwas partitioned between 5 M NaOH (10 mL) and chloroform (20 mL)
6. extractionThe aqueous layer was extracted with chloroform (20 mL)
7. dry with materialwere dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. additiona 90:10 mixture of the cis and trans amines

ORD record

ord-71921d4e814b4b6899170a93e46c4437

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08084462B2