反应详情

A mixture of (2R)-4-[5-(2-methoxycarbonyl-vinyl)-3-trifluoromethyl-pyridin-2-yl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester from step (d) above (6.02 g, 14 mmol), OsO4 (4.43 mL, 0.7 mmol, 4% in H2O, Aldrich) and N-methylmorpholine N-oxide (1.96 g, 16.8 mmol, Aldrich) in acetone (16 mL) was stirred at room temperature for 5 h. To the mixture was added saturated aqueous solution of NaHSO3 (910 mL) and the mixture was extracted with EtOAc (2×40 mL). The combined organic extracts were washed with brine (20 mL), dried over Na2SO4 and filtered. The filtrate was evaporated in vacuo and the residue was dissolved in dichloromethane (20 mL). To the solution was added Pb(OAc)4 (7.44 g, 16.8 mmol, Aldrich) in one portion and the mixture was stirred at 0° C. for 30 min. The mixture was diluted with hexane (10 mL), filtered through a Celite® pad and the filter cake was washed with 50% EtOAc/hexane. The filtrate was evaporated in vacuo and the residue was purified by silica gel column chromatography, eluting with 30% EtOAc/hexane to give the title compound as a gum. MS (ESI, pos. ion) m/e: 374 (M+1).

1. extractionthe mixture was extracted with EtOAc (2×40 mL)
2. washThe combined organic extracts were washed with brine (20 mL)
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. customThe filtrate was evaporated in vacuo
6. dissolutionthe residue was dissolved in dichloromethane (20 mL)
7. stirringthe mixture was stirred at 0° C. for 30 min
8. filtrationfiltered through a Celite® pad
9. washthe filter cake was washed with 50% EtOAc/hexane
10. customThe filtrate was evaporated in vacuo
11. customthe residue was purified by silica gel column chromatography
12. washeluting with 30% EtOAc/hexane