n-Butyl lithium → 4-Methylene-1-phenylpiperidine

Temperature

0 °C

In a 50 mL round bottom flask, methyltriphenylphosphonium iodide (1.384 g, 3.42 mmol) was suspended in THF (10.0 mL) and cooled to 0° C. N-Butyllithium (1.370 mL, 3.42 mmol) was added drop-wise and the resulting yellow suspension was stirred at 0° C. for 30 min. A solution of 1-phenylpiperidin-4-one (0.500 g, 2.85 mmol) in THF (5.0 mL) was added drop-wise and the orange, yellow suspension was then allowed to slowly warm to 23° C. over 2 hr. The reaction mixture was quenched with sat. NH4Cl (30 mL), the aq. layer was extracted with EtOAc (2×50 mL) and the combined organic extracts were washed with brine (30 mL), dried over MgSO4, filtered, and concentrated in vacuo. The crude yellow oil was purified by flash chromatography (EtOAc:Hex, 1:9 isocratic) affording the title compound as a clear, light yellow oil (0.0906 g, 18.33% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.14-2.39 (m, 4H) 3.12-3.29 (m, 4 H) 4.74 (s, 2H) 6.64-6.85 (m, 1H) 6.87-7.07 (m, 2H) 7.08-7.29 (m, 2H). ESI-MS: m/z 174.1 (M+H)+.

1. temperatureto slowly warm to 23° C. over 2 hr
2. customThe reaction mixture was quenched with sat. NH4Cl (30 mL)
3. extractionthe aq. layer was extracted with EtOAc (2×50 mL)
4. washthe combined organic extracts were washed with brine (30 mL)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude yellow oil was purified by flash chromatography (EtOAc:Hex, 1:9 isocratic)

ORD record

ord-8434510e0db3442bb3a59d134a590401

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08669249B2