Sodium hydride → {4-[(R)-2-Oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-but-2-ynyloxy}-acetonitrile

HRID 349373Notes

Reaction equation

HRID 349373 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.[CH:19]([C@H:21]1[CH2:26][CH2:25][CH2:24][C:23](=[O:27])[N:22]1[CH2:28][C:29]#[C:30][CH2:31][O:32][CH2:33][C:34]#[N:35])=O>C1COCC1>[O:27]=[C:23]1[CH2:24][CH2:25][CH2:26][C@H:21](/[CH:19]=[CH:5]/[C:4](=[O:3])[CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:22]1[CH2:28][C:29]#[C:30][CH2:31][O:32][CH2:33][C:34]#[N:35]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 12805884Dimethyl-2-oxo-3-phenylpropyl phosphonateHCID 86595301[4-((R)-2-formyl-6-oxo-piperidin-1-yl)-but-2-ynyloxy]-acetonitrile

Product 1

HCID 69020894{4-[(R)-2-Oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-but-2-ynyloxy}-acetonitrileYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (60% dispersion in oil, 18 mg, 0.45 mmol) was added to a solution of dimethyl 2-oxo-3-phenylpropylphosphonate (110 mg, 0.45 mmol) in THF (1.5 mL) at 0° C. After 1 h at 0° C., a solution of [4-((R)-2-formyl-6-oxo-piperidin-1-yl)-but-2-ynyloxy]-acetonitrile (0.50 mmol, crude from step 5) in THF (1.5 mL) was added via cannula. The reaction was allowed to warm to rt. After 18 h at rt, the reaction was quenched with aqueous acetic acid (50%, 10 mL) and extracted with EtOAc (3×20 mL). The combined organic phase was washed with brine (25 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (10% →40% EtOAc/CH2Cl2, gradient) afforded 75 mg (48%) of the title compound.

Workup

  1. waitAfter 18 h at rt
  2. customthe reaction was quenched with aqueous acetic acid (50%, 10 mL)
  3. extractionextracted with EtOAc (3×20 mL)
  4. washThe combined organic phase was washed with brine (25 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by flash column chromatography on silica gel (10% →40% EtOAc/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-e97f8c03ab864a2c9302c69e2412cc0c
Source dataset
uspto-grants-2007_02
Patent number
US07179820B2

Reaction notes

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