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

HRID 349301노트

반응식

HRID 349301 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-36f24ceb14f14f229cc5d461600e39d6
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07179820B2

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