Dimethylformamide → 5-iodo-1-(3-piperidin-1-yl-propyl)-1H-pyridin-2-one

HRID 991502Notes

Reaction equation

HRID 991502 reaction equation
[H-].[Na+].[I:3][C:4]1[CH:5]=[N:6][CH:7]=[C:8](O)[CH:9]=1.Cl.Cl[CH2:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.CN(C=[O:26])C>O>[I:3][C:4]1[CH:9]=[CH:8][C:7](=[O:26])[N:6]([CH2:13][CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH:5]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 79624N-(3-chloropropyl)piperidine hydrochlorideHCID 104891455-Iodopyridin-3-ol

Product 1

HCID 120181725-iodo-1-(3-piperidin-1-yl-propyl)-1H-pyridin-2-oneYield 40%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (0.073 g, 3.0 mmol) was stirred in 4 mL anhydrous DMF under Ar. The solution was cooled to 0° C. and 3-iodo-5-hydroxypyridine (0.305 g, 1.38 mmol) was added gradually. After bubbling had subsided N-chloropropylpiperidine hydrochloride (0.330 g, 1.67 mmol) was added slowly. The reaction was then allowed to warm to ambient temperature. After 40 h the reaction was diluted with water and extracted 3× with EtOAc. The combined organic phases were washed was washed with saturated NaCl (aq), dried over Na2SO4, filtered and concentrated. Purification by flash column chromatography (2×16 cm silica, 9:1 CH2Cl2/MeOH) afforded 192 mg 5-iodo-1-(3-piperidin-1-yl-propyl)-1H-pyridin-2-one (18) (40% yield). 1H NMR (CDCl3) δ7.72 (d, J=2.6 Hz, 1H), 7.40 (dd, J=2.6, 9.5 Hz, 1H), 6.37 (d, J=9.5 Hz, 1H), 3.96 (t, J=6.6 Hz, 2H), 2.35 (bs, 4H), 2.26 (t, J=6.6 Hz, 2H), 1.92 (t, 6.6 Hz, 2H), 1.60 (m, 4H), 1.46 (m, 2H).

Workup

  1. customAfter bubbling
  2. additionwas added slowly
  3. temperatureto warm to ambient temperature
  4. extractionextracted 3× with EtOAc
  5. washThe combined organic phases were washed
  6. washwas washed with saturated NaCl (aq)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by flash column chromatography (2×16 cm silica, 9:1 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-907b13b5ac91499ba25f3d42d9700b8c
Source dataset
uspto-grants-2002_10
Patent number
US06465484B1

Reaction notes

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