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

HRID 991502노트

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HRID 991502 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 962Water용매

반응 조건

온도
0 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-907b13b5ac91499ba25f3d42d9700b8c
출처 데이터셋
uspto-grants-2002_10
특허 번호
US06465484B1

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