Sodium hydride → {(Z)-4-[(R)-2-Oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-but-2-enyloxy}-acetic acid methyl ester

HRID 2052943Notes

Reaction equation

HRID 2052943 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][O:23][CH2:24]/[CH:25]=[CH:26]\[CH2:27][N:28]1[C:33](=[O:34])[CH2:32][CH2:31][CH2:30][C@@H:29]1[CH:35]=O>C1COCC1>[CH3:19][O:20][C:21](=[O:37])[CH2:22][O:23][CH2:24]/[CH:25]=[CH:26]\[CH2:27][N:28]1[C@@H: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 86595298[(Z)-4-((R)-2-formyl-6-oxo-piperidin-1-yl)-but-2-enyloxy]-acetic acid methyl ester

Product 1

HCID 60023029{(Z)-4-[(R)-2-Oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-but-2-enyloxy}-acetic acid methyl esterYield 42.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (60% dispersion in oil, 22 mg, 0.55 mmol) was added to a solution of dimethyl 2-oxo-3-phenylpropylphosphonate (135 mg, 0.56 mmol) in THF (1.0 mL) at 0° C. After 1 h at 0° C., [(Z)-4-((R)-2-formyl-6-oxo-piperidin-1-yl)-but-2-enyloxy]-acetic acid methyl ester (150 mg, 0.56 mmol) in THF (1 mL) was added via cannula. The reaction was allowed to warm to rt. After 16.5 h at rt, the reaction was quenched with saturated aqueous NH4Cl (15 mL) and extracted with EtOAc (3×15 mL). The combined organic phase was washed with brine (20 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (30%→60% EtOAc/CH2Cl2, gradient) afforded 91 mg (42%) of the title compound.

Workup

  1. waitAfter 16.5 h at rt
  2. customthe reaction was quenched with saturated aqueous NH4Cl (15 mL)
  3. extractionextracted with EtOAc (3×15 mL)
  4. washThe combined organic phase was washed with brine (20 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by flash column chromatography on silica gel (30%→60% EtOAc/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-fa781c231fbd495183508cf5d127b187
Source dataset
uspto-grants-2008_02
Patent number
US07326716B2

Reaction notes

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