Sodium hydride → 7-[(R)-2-oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-hept-5-ynoic acid methyl ester

Sodium hydride (60% dispersion in oil, 3.8 mg, 0.095 mmol) was added to a solution of dimethyl 2-oxo-3-phenylpropylphosphonate (21 mg, 0.087 mmol) in THF (0.5 mL) at 0° C. After 1 h at 0° C. rt, 7-((R)-2-formyl-6-oxo-piperidin-1-yl)-hept-5-ynoic acid methyl ester (prepared in accordance with example 7, step 1, crude, ˜0.095 mmol) in THF (0.5 mL) was added via cannula. The reaction was allowed to warm to rt. After 17.5 h at rt, the reaction was quenched with acetic acid (50% aqueous, 5 mL) and extracted with EtOAc (3×5 mL). The combined organic phase was washed brine (10 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→30% EtOAc/CH2Cl2, gradient) afforded 14 mg (42%) of 7-[(R)-2-oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-hept-5-ynoic acid methyl ester.

1. customthe reaction was quenched with acetic acid (50% aqueous, 5 mL)
2. extractionextracted with EtOAc (3×5 mL)
3. washThe combined organic phase was washed brine (10 mL)
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customPurification of the residue by flash column chromatography on silica gel (CH2Cl2→30% EtOAc/CH2Cl2, gradient)

ORDレコード

ord-68d3d74bb637408b86bae32eb6a961f5

出典データセット

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07179820B2