反应详情

温度

83 °C

To 3-fluoro-6-methoxy-N-((4-methyltetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine in acetonitrile (12 mL) was added sodium iodide (4.24 g, 28.3 mmol) and slowly TMS-Cl (3.62 mL, 28.3 mmol). The mixture was heated to reflux (oil bath: 83° C.) for 4 hr. The mixture was allowed to cool to ambient temperature and was diluted with EtOAc and saturated aqueous NaHCO3 solution. The mixture was vigorously stirred for 15 min and acidified with 0.5N aqueous NaHSO4 solution and stirring was continued for 5 min. The mixture was neutralized with saturated aqueous NaHCO3 solution. The separated aqueous phase was extracted with EtOAc (3×). The combined organic layers were dried over sodium sulfate, filtered off and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 40 g, 25 min, EtOAc/heptane=5/95 for 2 min, 5/95 to 50/50 over 18 min, then 50/50] providing 5-fluoro-6-((4-methyltetrahydro-2H-pyran-4-yl)methyl)aminopyridin-2-ol as colorless highly viscous oil. Yield: 420 mg. LCMS (m/z): 241.1 [M+H]+; Retention time=0.55 min.

1. temperatureThe mixture was heated
2. temperatureto cool to ambient temperature
3. stirringstirring
4. waitwas continued for 5 min
5. extractionThe separated aqueous phase was extracted with EtOAc (3×)
6. dry with materialThe combined organic layers were dried over sodium sulfate
7. filtrationfiltered off
8. concentrationconcentrated in vacuo
9. customThe resulting residue was purified by column chromatography [SiO2, 40 g, 25 min, EtOAc/heptane=5/95 for 2 min
10. wait5/95 to 50/50 over 18 min