Sodium hydride → 7-[2-Oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-hept-5-ynoic acid methyl ester

HRID 352416노트

반응식

HRID 352416 반응식
[H-].[Na+].[O:3]=[C:4]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:5]P(=O)(OC)OC.[CH3:19][O:20][C:21](=[O:37])[CH2:22][CH2:23][CH2:24][C:25]#[C:26][CH2:27][N:28]1[C:33](=[O:34])[CH2:32][CH2:31][CH2:30][CH:29]1[CH:35]=O>C1COCC1>[CH3:19][O:20][C:21](=[O:37])[CH2:22][CH2:23][CH2:24][C:25]#[C:26][CH2:27][N:28]1[CH:29](/[CH:35]=[CH:5]/[C:4](=[O:3])[CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:30][CH2:31][CH2:32][C:33]1=[O:34]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 12805884Dimethyl-2-oxo-3-phenylpropyl phosphonateHCID 860125007-(2-Formyl-6-oxo-piperidin-1-yl)-hept-5-ynoic acid methyl ester

생성물 1

HCID 104749617-[2-Oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-hept-5-ynoic acid methyl ester수율 21%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

Sodium hydride (60% dispersion in oil, 23 mg, 0.58 mmol) was added to a solution of dimethyl 2-oxo-3-phenylpropylphosphonate (171 mg, 0.64 mmol) in THF (2.0 mL) at 0° C. After 10 min at 0° C., the solution was allowed to warm to rt. After 50 min at rt, the solution was recooled to 0° C. and 7-(2-formyl-6-oxo-piperidin-1-yl)-hept-5-ynoic acid methyl ester (crude, prepared in accordance with example 1, step 4, ˜0.64 mmol) in THF (2.0 mL) was added via cannula. The reaction was allowed to warm to rt. After 18 h at rt, the reaction was quenched with acetic acid (50% aqueous, 20 mL) and extracted with EtOAc (30×20 mL). The combined organic phase was washed with saturated aqueous NaHCO3 (30 mL) and brine (30 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel twice (1st CH2Cl2→2% MeOH/CH2Cl2, gradient and 2nd CH2Cl2→30% EtOAc/CH2Cl2, gradient) afforded 51 mg (21%) of the title compound.

후처리

  1. waitAfter 50 min at rt
  2. customwas recooled to 0° C.
  3. temperatureto warm to rt
  4. waitAfter 18 h at rt
  5. customthe reaction was quenched with acetic acid (50% aqueous, 20 mL)
  6. extractionextracted with EtOAc (30×20 mL)
  7. washThe combined organic phase was washed with saturated aqueous NaHCO3 (30 mL) and brine (30 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by flash column chromatography on silica gel twice (1st CH2Cl2→2% MeOH/CH2Cl2, gradient and 2nd CH2Cl2→30% EtOAc/CH2Cl2, gradient)

출처 및 근거

ORD 기록
ord-9a47cb8cfa004d0f88d23af0fc6c823c
출처 데이터셋
uspto-grants-2004_06
특허 번호
US06747037B1

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