Sodium Chloride → 2-(Phenylmethyl)-2-azabicyclo[2.2.2]octane

Temperature

0 °C

To a vigorously stirring suspension of p-fluorobenzyltriphenylphosphonium chloride (5.7 g, 14 mmol, Aldrich) in dry tetrahydrofuran (30 mL) at −78° C. was added 2.5 M n-butyllithium (4.7 mL, 12 mmol) in hexanes via syringe. After 30 min, the orange-yellow mixture was warmed to 0° C., and the suspension became deep red. After 5 min, 2-benzyl-2-azabicyclo[2.2.2]octan-6-one (1.2 g, 5.6 mmol) was added as a solution in dry tetrahydrofuran (25 mL) via cannula. Upon stirring vigorously for 2.5 hrs, the reaction was poured into saturated aqueous sodium chloride (70 mL), and the aqueous layer was extracted with ethyl acetate (3×70 mL). The combined organic layers were washed with saturated aqueous sodium chloride (50 mL), dried over sodium sulfate, and concentrated in vacuo. The resulting yellow solid was purified by flash chromatography (20%-70% ethyl acetate in hexanes) to yield 6-[4-fluorophenyl)methylene]-2-(phenylmethyl)-2-azabicyclo[2.2.2]octane (1.7 g, 99%) as a pale yellow oil. MS (ESI) 308 (M+H).

1. waitAfter 5 min
2. stirringUpon stirring vigorously for 2.5 hrs
3. extractionthe aqueous layer was extracted with ethyl acetate (3×70 mL)
4. washThe combined organic layers were washed with saturated aqueous sodium chloride (50 mL)
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated in vacuo
7. customThe resulting yellow solid was purified by flash chromatography (20%-70% ethyl acetate in hexanes)

ORD record

ord-f66f5f4791a346c394103634f3a9fed3

Source dataset

uspto-grants-2003_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06586446B1