反应详情

To a solution of 0.325 g (0.73 mmol) of (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)piperidin-2-one (Example 68, Step B) and iodomethane (0.055 mL, 0.874 mmol) in THF (7.0 mL) was added lithium bis(trimethylsilyl) amide (1M solution in THF, 0.8 mL, 0.8 mmol) at −78° C. The reaction was allowed to warm to R.T., then was quenched with sat. aqueous NH4Cl solution and extracted with EtOAc. The combined organic layers were washed with water and sat. aq. NaCl solution, dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. The crude material was absorbed onto a plug of silica gel and purified by chromatography on silica gel, eluting with a gradient of 10% to 30% EtOAc in hexane, to provide the title compound as a mixture of C-3 stereoisomers, as indicated by *.

1. customwas quenched with sat. aqueous NH4Cl solution
2. extractionextracted with EtOAc
3. washThe combined organic layers were washed with water and sat. aq. NaCl solution
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationthe filtrate was concentrated under reduced pressure
7. customThe crude material was absorbed onto a plug of silica gel
8. custompurified by chromatography on silica gel
9. washeluting with a gradient of 10% to 30% EtOAc in hexane