反应详情

温度

0 °C

To a −78° C. solution of 3.19 g (5.05 mmol) of (5R,6S)-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)piperidin-2-one (Example 121, Step I) and 347 μL (5.55 mmol) of methyl iodide in dry, degassed THF (40 mL) was added 6.82 mL (6.82 mmol) of a 1 M solution of lithium bis(trimethylsilyl)amide in THF slowly via syringe over 2 min. The yellow solution was warmed to 0° C. and stirred for 1.5 h, and then was warmed to room temperature and stirred for an additional 15 min. The reaction was quenched with saturated aqueous ammonium chloride, and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by flash chromatography on silica gel (0-15% MeOH/DCM, gradient elution) provided the title compound (mixture of C-3 epimers) as a white solid.

1. customdegassed THF (40 mL)
2. additionwas added 6.82 mL (6.82 mmol) of a 1 M solution of lithium bis(trimethylsilyl)amide in THF slowly via syringe over 2 min
3. temperaturewas warmed to room temperature
4. stirringstirred for an additional 15 min
5. customThe reaction was quenched with saturated aqueous ammonium chloride
6. extractionextracted with EtOAc (3×)
7. dry with materialThe combined organic layers were dried over Na2SO4
8. filtrationfiltered
9. concentrationthe filtrate was concentrated
10. customPurification of the residue by flash chromatography on silica gel (0-15% MeOH/DCM, gradient elution)