Sodium hydride → HCID 66791198, compound

HRID 2114749Notes

Reaction equation

HRID 2114749 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][S:25][CH2:26][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][CH2:23][CH2:24][S:25][CH2:26][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 86609573HCID 86609573, compound

Product 1

HCID 66791198HCID 66791198, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (60% dispersion in oil, 4.4 mg, 0.11 mmol) was added to a solution of dimethyl 2-oxo-3-phenylpropylphosphonate (26.5 mg, 0.11 mmol) in THF (0.7 mL) at 0° C. After 1 h at 0° C., the mixture of aldehydes from step 4 above (˜0.10 mmol) in THF (0.5 mL) was added via cannula. The reaction was allowed to warm to room temperature. After 18 h at room temperature, the reaction was quenched with aqueous acetic acid (50%, 5 mL) and extracted with EtOAc (3×5 mL). The combined organic phase was washed with brine (10 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (20%→60% EtOAc/CH2Cl2, gradient) followed by preparative thin layer chromatography (silica, 5% MeOH/CH2CI2) afforded 6.8 mg (16%) of 4-{2-[(R)-2-oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-ethylsulfanyl }-butyric acid methyl ester.

Workup

  1. additionwas added via cannula
  2. waitAfter 18 h at room temperature
  3. customthe reaction was quenched with aqueous acetic acid (50%, 5 mL)
  4. extractionextracted with EtOAc (3×5 mL)
  5. washThe combined organic phase was washed with brine (10 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by flash column chromatography on silica gel (20%→60% EtOAc/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-cd86e36cbc474ff39ff93af9c486311d
Source dataset
uspto-grants-2008_10
Patent number
US07435746B2

Reaction notes

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