Sodium hydride → 7-[2-Oxo-6-((E)-3-oxo-oct-1-enyl)-piperidin-1-yl]-heptanoic acid methyl ester

HRID 352411ノート

反応式

HRID 352411 の反応式
[H-].[Na+].[O:3]=[C:4]([CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:5]P(=O)(OC)OC.[CH3:17][O:18][C:19](=[O:35])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][N:26]1[C:31](=[O:32])[CH2:30][CH2:29][CH2:28][CH:27]1[CH:33]=O>C1COCC1>[CH3:17][O:18][C:19](=[O:35])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][N:26]1[CH:27](/[CH:33]=[CH:5]/[C:4](=[O:3])[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:28][CH2:29][CH2:30][C:31]1=[O:32]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 580181Dimethyl (2-oxoheptyl)phosphonateHCID 859731487-(2-Formyl-6-oxo-piperidin-1-yl)-heptanoic acid methyl ester

生成物 1

HCID 103842437-[2-Oxo-6-((E)-3-oxo-oct-1-enyl)-piperidin-1-yl]-heptanoic acid methyl ester収率 106.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

Sodium hydride (60% dispersion in oil, 15 mg, 0.37 mmol) was added to a solution of dimethyl 2-oxoheptylphosphonate (87 mg, 0.33 mmol) in THF (2 mL) at 0° C. After 10 min at 0° C., the solution was allowed to warm to rt. After 1 h at rt, the solution was recooled to 0° C. and 7-(2-formyl-6-oxo-piperidin-1-yl)-heptanoic acid methyl ester (crude from previous reaction, ˜0.37 mmol) in THF (2 mL) was added via cannula. The reaction was allowed to warm to rt. After 17 h at rt, the reaction was quenched with acetic acid (50% aqueous, 20 mL) and extracted with EtOAc (3×20 mL). The combined organic phase was washed with saturated aqueous NaHCO3 (20 mL) and brine (20 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→2% MeOH/CH2Cl2, gradient) afforded 128 mg (95%) of the title compound.

後処理

  1. waitAfter 1 h at rt
  2. customwas recooled to 0° C.
  3. temperatureto warm to rt
  4. waitAfter 17 h at rt
  5. customthe reaction was quenched with acetic acid (50% aqueous, 20 mL)
  6. extractionextracted with EtOAc (3×20 mL)
  7. washThe combined organic phase was washed with saturated aqueous NaHCO3 (20 mL) and brine (20 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by flash column chromatography on silica gel (CH2Cl2→2% MeOH/CH2Cl2, gradient)

出典と根拠

ORDレコード
ord-d4538fb43b62428da76bda83f9516db9
出典データセット
uspto-grants-2004_06
特許番号
US06747037B1

反応ノート

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