反应详情

温度

0 °C

To a pre-cooled 0° C. solution of tert-butyl[(3S,5S)-5-(2-fluorophenyl)-2-oxopiperidin-3-yl]carbamate (0.85 g, 2.76 mmol) in tetrahydrofuran:N-methyl-2-pyrrolidinone (2:1, 18 mL) was added lithium bis(trimethylsilyl)amide (3.58 mL, 3.58 mmol, 1 M in THF) and the mixture was stirred at 0° C. for 30 min. 1-Iodo-2-methylpropane (0.48 mL, 4.13 mmol) was added and the resulting mixture was stirred at 0° C. for 2 h and then warmed to 23° C. and stirred for an additional 18 h. The mixture was diluted with water and extracted with ethyl acetate (3×). The combined organic extracts were washed with water, brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (0% ethyl acetate→70% ethyl acetate/hexane) was followed by separation of the cis/trans diastereomers using supercritical fluid chromatography with a ChiralPak® AD column and eluting with 20% ethanol in carbon dioxide to afford the title compound as the second diastereomer to elute. MS: m/z=387.2 (M+Na).

1. stirringthe resulting mixture was stirred at 0° C. for 2 h
2. temperaturewarmed to 23° C.
3. stirringstirred for an additional 18 h
4. extractionextracted with ethyl acetate (3×)
5. washThe combined organic extracts were washed with water, brine
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customPurification by silica gel chromatography (0% ethyl acetate→70% ethyl acetate/hexane)
10. customwas followed by separation of the cis/trans diastereomers
11. washeluting with 20% ethanol in carbon dioxide