1-(4-Chlorophenyl)piperidin-4-one → 1-(4-Chlorophenyl)-4-methylenepiperidine

Temperature

-78 °C

Methyltriphenylphosphonium bromide (1.429 g, 4.00 mmol) was suspended in THF (Ratio: 1.667, Volume: 2.5 ml) and cooled to −78° C. n-butyllithium (0.960 ml, 2.400 mmol) was added dropwise over 3 min and the resulting yellow suspension was stirred at −78° C. for 10 min. A solution of 1-(4-chlorophenyl)piperidin-4-one (0.419 g, 2 mmol) in THF (Ratio: 1.000, Volume: 1.5 ml) was added dropwise over 3 min and the dark red suspension was stirred at −78° C. for 10 min and then allowed to slowly warm to 5° C. over 1 h. The reaction was stirred at 5° C. for 4 h and was quenched with water (4 mL). This was extracted with ethyl ether (2×5 mL) and the extracts were washed with water (4×5 mL). The combined water washes were back-extracted with ethyl ether (5 mL) and the combined organic extracts were washed with brine (5 ml), dried (MgSO4), filtered and concentrated in vacuo. Flash column chromatography (40 g SiO2, hexanes:ethyl acetate 9:1) afforded 1-(4-chlorophenyl)-4-methylenepiperidine (0.196 g, 0.944 mmol, 47.2% yield) as a clear yellow oil. [M+H] calc'd for C12H14Cl, 208; found, 208.

1. additionwas added dropwise over 3 min
2. stirringthe dark red suspension was stirred at −78° C. for 10 min
3. temperatureto slowly warm to 5° C. over 1 h
4. stirringThe reaction was stirred at 5° C. for 4 h
5. customwas quenched with water (4 mL)
6. extractionThis was extracted with ethyl ether (2×5 mL)
7. washthe extracts were washed with water (4×5 mL)
8. extractionThe combined water washes were back-extracted with ethyl ether (5 mL)
9. washthe combined organic extracts were washed with brine (5 ml)
10. dry with materialdried (MgSO4)
11. filtrationfiltered
12. concentrationconcentrated in vacuo

ORD record

ord-10f1a5ce485b48358892cbbff6e2df8b

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08822470B2