Sodium hydride → (S)-Methyl 2-((3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-1-yl)butanoate

Temperature

0 °C

To a solution of 1.3 g (3.61 mmol) of(3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one (Example 42, Step A) in DMF (14.43 mL) at 0° C. was added a dispersion of 60% sodium hydride in mineral oil (0.361 g, 9.02 mmol). The grey slurry was stirred at 0° C. for 30 minutes. Then methyl 2-bromobutanoate (1.246 mL, 10.83 mmol) was added. The mixture was warmed to room temperature and stirred at room temperature for 1 h. The mixture was quenched with sat. NH4Cl. The mixture was extracted with ethyl acetate. The organic layer was washed with water, 1 M LiCl (2×), and sat. aq. NaCl solution. The organic layer was dried over Na2SO4 filtered and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (80 g column; eluent: 10 to 35% EtOAc in hexanes) to give the title compound as the less polar, major diastereomer.

1. temperatureThe mixture was warmed to room temperature
2. stirringstirred at room temperature for 1 h
3. customThe mixture was quenched with sat. NH4Cl
4. extractionThe mixture was extracted with ethyl acetate
5. washThe organic layer was washed with water, 1 M LiCl (2×), and sat. aq. NaCl solution
6. dry with materialThe organic layer was dried over Na2SO4
7. filtrationfiltered
8. concentrationthe filtrate was concentrated under reduced pressure
9. customThe residue was purified by flash chromatography on silica gel (80 g column; eluent: 10 to 35% EtOAc in hexanes)

ORD record

ord-ab488442e9e0416e920bad63d344147f

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296736B2