反应详情

Sodium hydride (60% dispersion in oil, 15 mg, 0.39 mmol) was added to a solution of [3-(3-chlorophenyl)-2-oxopropyl]-phosphonic acid dimethyl ester (97 mg, 0.35 mmol) in THF (1.5 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 (0.37 mmol, crude) in THF (1.5 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%, 15 mL) and extracted with EtOAc (3×15 mL). The combined organic phase was washed with brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (20% →30% EtOAc/CH2Cl2, gradient) afforded 100 mg (68%) of the title compound.

1. waitAfter 18 h at rt
2. customthe reaction was quenched with aqueous acetic acid (50%, 15 mL)
3. extractionextracted with EtOAc (3×15 mL)
4. washThe combined organic phase was washed with brine (20 mL)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customPurification of the residue by flash column chromatography on silica gel (20% →30% EtOAc/CH2Cl2, gradient)