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

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.

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)

ORDレコード

ord-5f39fa0221234fcdb013fb706325e838

出典データセット

uspto-grants-2008_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07326716B2