反应详情

温度

-10 °C

To a slurry of 1-Acetyl-piperidine-4-carboxylic acid [2-(4-fluoro-phenyl)-1-hydroxymethyl-2-oxo-ethyl]-amide, prepared as in Part B, (100 g, 0.30 mol) and pyridine (100 mL, 1.20 mole) in dichloromethane (900 mL) at -40° C. is added trifluoroacetic anhydride (200 mL, 1.40 mole) over 1.5 hrs. The reaction is allowed to warm to -10° C. over 2 hrs and stirred at -10° C. for 1.5 hrs. Water (200 mL) is added, keeping the temperature at 0°--5° C. The layers are separated and the dichloromethane is washed with water (6×400 mL), dried (MgSO4) and concentrated to a yellow oil. The oil is taken up in methanol (600 mL) and silica gel (100 g) is added and the mixture stirred at 20° C. for 16 hrs. The silica gel is removed by filtration, rinsed with methanol (400 mL) and the filtrate is concentrated. Ether (500 mL) is added to the residue and stirred for 2 hrs and the resulting solid is filtered to afford 1-(4-[5-(4-fluoro-phenyl)-4-hydroxymethyl-oxazol-2-yl]-piperidin-1-yl)-ethanone as a pale yellow solid.

1. customat 0°--5° C
2. customThe layers are separated
3. washthe dichloromethane is washed with water (6×400 mL)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated to a yellow oil
6. additionsilica gel (100 g) is added
7. stirringthe mixture stirred at 20° C. for 16 hrs
8. customThe silica gel is removed by filtration
9. washrinsed with methanol (400 mL)
10. concentrationthe filtrate is concentrated
11. additionEther (500 mL) is added to the residue
12. stirringstirred for 2 hrs
13. filtrationthe resulting solid is filtered