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

HRID 349306Notes

Reaction equation

HRID 349306 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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 (3×20 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.

Workup

  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 (3×20 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)

Sources & evidence

ORD record
ord-948eb9c81ee34812998bc9ee7d7b4935
Source dataset
uspto-grants-2007_02
Patent number
US07179820B2

Reaction notes

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