Methyl iodide → 3-Bromo-4-(methoxymethyl)pyridine

To an ice-cold solution of Intermediate 65A (1.0 g, 5.32 mmol) in THF (Volume: 26.6 ml) was added sodium hydride (0.255 g, 6.38 mmol). The ice bath was removed and the reaction mixture was allowed to stir at room temperature for 30 min, then cooled to 0° C. and followed by addition of methyl iodide (0.366 ml, 5.85 mmol). The ice bath was removed and the reaction mixture was allowed to stir at room temperature for 16 hours. The reaction mixture was then quenched with water and concentrated to remove the THF. The resulting aqueous layer was extracted with DCM (3×). The combined organics were washed with water and brine, dried, and concentrated to give an oil. The oil was purified by silica gel chromatography (hexane: ethyl acetate 70:30) to afforded the title compound as a colorless oil. MS (ES): m/z=203.9 [M+H]+. Intermediate 65 was used in the synthesis of Example 254.

1. customThe ice bath was removed
2. temperaturecooled to 0° C.
3. customThe ice bath was removed
4. stirringto stir at room temperature for 16 hours
5. customThe reaction mixture was then quenched with water
6. concentrationconcentrated
7. customto remove the THF
8. extractionThe resulting aqueous layer was extracted with DCM (3×)
9. washThe combined organics were washed with water and brine
10. customdried
11. concentrationconcentrated
12. customto give an oil
13. customThe oil was purified by silica gel chromatography (hexane: ethyl acetate 70:30)

ORD record

ord-5f634f5e4373455a85777340101f22a3

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08916553B2