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

Sodium hydride (60% dispersion in oil, 37 mg, 0.91 mmol) was added to a solution of dimethyl 2-oxoheptylphosphonate (217 mg, 0.83 mmol) in THF (4 mL) at 0° C. After 10 min at 0° C., the solution was allowed to warm to rt. After 50 min at rt, the solution was recooled to 0° C. and 7-(2-formyl-6-oxo-piperidin-1-yl)-hept-5-ynoic acid methyl ester (crude from previous reaction, ˜0.92 mmol) in THF (2 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 and water (1:1, 15 mL) and extracted with EtOAc (3×40 mL). The combined organic phase was washed with brine (50 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (10% →50% EtOAc/CH2Cl2, gradient) afforded 175 mg (58%) of the title compound.

1. waitAfter 50 min 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 and water (1:1, 15 mL)
6. extractionextracted with EtOAc (3×40 mL)
7. washThe combined organic phase was washed with brine (50 mL)
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customPurification of the residue by flash column chromatography on silica gel (10% →50% EtOAc/CH2Cl2, gradient)

ORDレコード

ord-d45aafa9b24347a4944f207d4a03ac9f

出典データセット

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06747037B1