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

HRID 991502ノート

反応式

HRID 991502 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-907b13b5ac91499ba25f3d42d9700b8c
出典データセット
uspto-grants-2002_10
特許番号
US06465484B1

反応ノート

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