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

HRID 349320

Reaktionsgleichung

Reaktionsgleichung von HRID 349320
[H-].[Na+].[O:3]=[C:4]([CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:5]P(=O)(OC)OC.[CH3:17][O:18][C:19](=[O:35])[CH2:20][CH2:21][CH2:22][C:23]#[C:24][CH2:25][N:26]1[C:31](=[O:32])[CH2:30][CH2:29][CH2:28][C@@H:27]1[CH:33]=O>C1COCC1>[CH3:17][O:18][C:19](=[O:35])[CH2:20][CH2:21][CH2:22][C:23]#[C:24][CH2:25][N:26]1[C@@H:27](/[CH:33]=[CH:5]/[C:4](=[O:3])[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:28][CH2:29][CH2:30][C:31]1=[O:32]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 580181Dimethyl (2-oxoheptyl)phosphonateHCID 865952957-((R)-2-formyl-6-oxo-piperidin-1-yl)-hept-5-ynoic acid methyl ester

Produkt 1

HCID 690237087-[(R)-2-oxo-6-((E)-3-oxo-oct-1-enyl)-piperidin-1-yl]-hept-5-ynoic acid methyl esterAusbeute 85,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

Sodium hydride (60% dispersion in oil, 8.8 mg, 0.22 mmol) was added to a solution of dimethyl 2-oxoheptylphosphonate (52 mg, 0.23 mmol) in THF (1 mL) at 0° C. After 10 min at 0° C., the solution was allowed to warm to rt. After 1 h at rt, the solution was recooled to 0° C. and 7-((R)-2-formyl-6-oxo-piperidin-1-yl)-hept-5-ynoic acid methyl ester (crude from previous reaction, ˜0.22 mmol) in THF (1 mL) was added via cannula. The reaction was allowed to warm to rt. After 18.5 h at rt, the reaction was quenched with aqueous acetic acid (50%, 5 mL) and extracted with EtOAc (3×10 mL). The combined organic phase was washed with saturated aqueous NaHCO3 (10 mL) and brine (10 mL) then dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→2% MeOH/CH2Cl2, gradient) afforded 68 mg (85%) of 7-[(R)-2-oxo-6-((E)-3-oxo-oct-1-enyl)-piperidin-1-yl]-hept-5-ynoic acid methyl ester.

Aufarbeitung

  1. waitAfter 1 h at rt
  2. customwas recooled to 0° C.
  3. temperatureto warm to rt
  4. waitAfter 18.5 h at rt
  5. customthe reaction was quenched with aqueous acetic acid (50%, 5 mL)
  6. extractionextracted with EtOAc (3×10 mL)
  7. washThe combined organic phase was washed with saturated aqueous NaHCO3 (10 mL) and brine (10 mL)
  8. dry with materialthen dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by flash column chromatography on silica gel (CH2Cl2→2% MeOH/CH2Cl2, gradient)

Quellen und Nachweise

ORD-Eintrag
ord-67ef38770a974285bed38c5bd8c41fb0
Quelldatensatz
uspto-grants-2007_02
Patentnummer
US07179820B2

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