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

HRID 2052929Notes

Reaction equation

HRID 2052929 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][C@@H: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[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 865952957-((R)-2-formyl-6-oxo-piperidin-1-yl)-hept-5-ynoic acid methyl ester

Product 1

HCID 690215987-[(R)-2-oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-hept-5-ynoic acid methyl esterYield 42.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (60% dispersion in oil, 3.8 mg, 0.095 mmol) was added to a solution of dimethyl 2-oxo-3-phenylpropylphosphonate (21 mg, 0.087 mmol) in THF (0.5 mL) at 0° C. After 1 h at 0° C. rt, 7-((R)-2-formyl-6-oxo-piperidin-1-yl)-hept-5-ynoic acid methyl ester (prepared in accordance with example 7, step 1, crude, ˜0.095 mmol) in THF (0.5 mL) was added via cannula. The reaction was allowed to warm to rt. After 17.5 h at rt, the reaction was quenched with acetic acid (50% aqueous, 5 mL) and extracted with EtOAc (3×5 mL). The combined organic phase was washed brine (10 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→30% EtOAc/CH2Cl2, gradient) afforded 14 mg (42%) of 7-[(R)-2-oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-hept-5-ynoic acid methyl ester.

Workup

  1. customthe reaction was quenched with acetic acid (50% aqueous, 5 mL)
  2. extractionextracted with EtOAc (3×5 mL)
  3. washThe combined organic phase was washed brine (10 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by flash column chromatography on silica gel (CH2Cl2→30% EtOAc/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-b58bd95ed7b84270a0d4825b588d7f58
Source dataset
uspto-grants-2008_02
Patent number
US07326716B2

Reaction notes

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