Sodium hydride → {4-[(R)-2-Oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-but-2-ynyloxy}-acetic acid methyl ester

Sodium hydride (60% dispersion in oil, 41 mg, 1.03 mmol) was added to a solution of dimethyl 2-oxo-3-phenylpropylphosphonate (247 mg, 1.02 mmol) in THF (4 mL) at 0° C. After 1 h at 0° C., a solution of [4-((R)-2-formyl-6-oxo-piperidin-1-yl)-but-2-ynyloxy]-acetic acid methyl ester (1.23 mmol, crude, prepared as in Example 69, step 4) in THF (3 mL) was added via cannula. The reaction was allowed to warm to rt. After 18 h at rt, the reaction was quenched with aqueous acetic acid (50%, 30 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 (30%→50% EtOAc/CH2Cl2, gradient) afforded 122 mg (31%) of the title compound.

1. waitAfter 18 h at rt
2. customthe reaction was quenched with aqueous acetic acid (50%, 30 mL)
3. extractionextracted with EtOAc (3×40 mL)
4. washThe combined organic phase was washed with brine (50 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%→50% EtOAc/CH2Cl2, gradient)

ORDレコード

ord-39663e8e683444daa527a243136badaf

出典データセット

uspto-grants-2008_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07326716B2