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

Sodium hydride (60% dispersion in oil, 8.2 mg, 0.21 mmol) was added to a solution of dimethyl 2-oxo-3-phenylpropylphosphonate (45 mg, 0.19 mmol) in THF (1.0 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)-heptanoic acid methyl ester (crude from previous reaction, ˜0.21 mmol) in THF (1.0 mL) was added via cannula. The reaction was allowed to warm to rt. After 18 h at rt, the reaction was quenched with acetic acid (50% aqueous, 10 mL) and extracted with EtOAc (3×15 mL). The combined organic phase was washed with saturated aqueous NaHCO3 (20 mL) and brine (20 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→2% MeOH/CH2Cl2, gradient) afforded 36.5 mg (51%) of 7-[(R)-2-oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-heptanoic acid methyl ester.

1. waitAfter 1 h at rt
2. customwas recooled to 0° C.
3. temperatureto warm to rt
4. waitAfter 18 h at rt
5. customthe reaction was quenched with acetic acid (50% aqueous, 10 mL)
6. extractionextracted with EtOAc (3×15 mL)
7. washThe combined organic phase was washed with saturated aqueous NaHCO3 (20 mL) and brine (20 mL)
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customPurification of the residue by flash column chromatography on silica gel (CH2Cl2→2% MeOH/CH2Cl2, gradient)

ORD-Eintrag

ord-7f53f54fb50c4a78bfef29add21b515e

Quelldatensatz

uspto-grants-2008_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07326716B2