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

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.

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)

ORD-Eintrag

ord-0b601375824d46fea114a918bd82d8bd

Quelldatensatz

uspto-grants-2005_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06977260B2