反应详情

温度

0 °C

Tebbe reagent (Bis(cyclopentadienyl)-μ-chloro(dimethylaluminum)-μ-methylenetitanium, 0.5 M solution in toluene, 1.7 mL, 0.85 mmol) was added dropwise over 5 minutes to a stirred solution of methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-1-oxobutan-2-yl)piperidin-3-yl)acetate (Example 415, Step A, 360 mg, 0.756 mmol) in toluene (4.7 mL) at 0° C. The reaction was stirred at 0° C. for 20 minutes and at rt for 30 minutes. The reaction was recooled to 0° C. and an additional portion of Tebbe reagent (0.5 M solution in toluene, 1 mL, 0.5 mmol) was added. The reaction was allowed to warm to rt for 20 minutes. The reaction was recooled to 0° C. and treated with sat. aq. NaHCO3 solution (40 mL) and EtOAc (100 mL). The separated aqueous layer was extracted with EtOAc (2×60 mL) and the combined organic extracts were washed with brine (80 ml), dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. Column chromatography on silca gel (24 g, SiO2, eluent: hexanes:EtOAc, 1:0 to 3:1, gradient elution) gave the title compound.

1. customwas recooled to 0° C.
2. temperatureto warm to rt for 20 minutes
3. customwas recooled to 0° C.
4. extractionThe separated aqueous layer was extracted with EtOAc (2×60 mL)
5. washthe combined organic extracts were washed with brine (80 ml)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationthe filtrate was concentrated under reduced pressure
9. washColumn chromatography on silca gel (24 g, SiO2, eluent: hexanes:EtOAc, 1:0 to 3:1, gradient elution)