反应详情

温度

95 °C

To a solution of 3-fluoro-6-methoxy-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine (4.6 g, 19.14 mmol) in acetonitrile (50 mL) was added sodium iodide (20.09 g, 134 mmol) and TMS-chloride (17.13 mL, 134 mmol). The resulting mixture was stirred at about 95° C. for 20 hr. The reaction mixture was cooled to ambient temperature and then diluted with EtOAc (80 mL) and water (40 mL). The diluted mixture was stirred vigorously for about 30 min. The organic layer was separated and washed with 0.1N aqueous HCl solution. The combined aqueous layers were carefully neutralized (pH ˜7) with solid NaHCO3 solution and extracted with EtOAc (1×100 mL) and DCM (2×50 mL). The combined organic layers were washed with saturated aqueous NaHCO3 solution and brine, dried over Na2SO4, filtered off and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 80 g, EtOAc/heptane=10/90 for 2 min, EtOAc/heptane=10/90 to 100/0 over 23 min, then EtOAc/heptane=100/0] providing 5-fluoro-6-((tetrahydro-2H-pyran-4-yl)methyl)aminopyridin-2-ol as a highly viscous oil which turned to purple upon standing at room temperature. Yield: 780 mg. LCMS (m/z): 227.1 [M+H]+; Retention time=0.42 min.

1. temperatureThe reaction mixture was cooled to ambient temperature
2. stirringThe diluted mixture was stirred vigorously for about 30 min
3. customThe organic layer was separated
4. washwashed with 0.1N aqueous HCl solution
5. extractionextracted with EtOAc (1×100 mL) and DCM (2×50 mL)
6. washThe combined organic layers were washed with saturated aqueous NaHCO3 solution and brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered off
9. concentrationconcentrated in vacuo
10. customThe resulting residue was purified by column chromatography [SiO2, 80 g, EtOAc/heptane=10/90 for 2 min
11. waitEtOAc/heptane=10/90 to 100/0 over 23 min