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 zinc chloride 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 sodium hydroxide (10 mL) and chloroform (20 mL). The aqueous layer was extracted with chloroform (20 mL), and combined organic layers were dried (sodium sulfate), filtered and concentrated. This left 2.97 g of yellow gum. GCMS analysis indicated that the product was a 1:9 mixture of the cis and trans amines, along with a trace of the corresponding alcohol (98% total 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 sodium hydroxide (10 mL) and chloroform (20 mL)
6. extractionThe aqueous layer was extracted with chloroform (20 mL)
7. dry with materialwere dried (sodium sulfate)
8. filtrationfiltered
9. concentrationconcentrated
10. additiona 1:9 mixture of the cis and trans amines

ORD record

ord-60b0c0f3e5694f5199e61afd20c1e827

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846715B2