2-Chloropyrimidine → 1-Pyrimidin-2-yl-piperidin-4-one

Temperature

80 °C

To a solution of 2-chloropyrimidine (300 mg, 2.619 mmol) in dioxane (5 ml), was added piperidin-4-one hydrochloride monohydrate (402.3 mg, 2.619 mmol) at room temperature. The mixture was heated at 80° C. overnight and concentrated under reduced pressure. The residue was treated with EtOAc (30 ml) and saturated NaHCO3 (10 ml). After separation of the layers, the aqueous phase was extracted with EtOAc (2×10 ml). The combined organic layers were washed with brine (10 ml), dried (MgSO4), filtered, and concentrated under reduced pressure to furnish a crude product. This material was purified by column chromatography (40% EtOAc/hexanes) to give 1-pyrimidin-2-yl-piperidin-4-one (320 mg, 53%) as an off-white solid: 1H NMR (CDCl3, 400 MHz) δ 8.38 (d, J=6.4 Hz, 2H), 6.61 (t, J=6.4 Hz, 9H), 4.16 (t, J=5.6 Hz, 2H), 2.53 (t, J=5.6 Hz, 2H).

1. concentrationconcentrated under reduced pressure
2. additionThe residue was treated with EtOAc (30 ml) and saturated NaHCO3 (10 ml)
3. customAfter separation of the layers
4. extractionthe aqueous phase was extracted with EtOAc (2×10 ml)
5. washThe combined organic layers were washed with brine (10 ml)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto furnish a crude product
10. customThis material was purified by column chromatography (40% EtOAc/hexanes)

ORD record

ord-b369c92272ea42f5b36121aa19dfa4b5

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772291B2