Sodium hydride → 3-Bromo-4-(cyclopropylmethoxy)pyridine

To an ice-cold solution of cyclopropylmethanol (0.562 g, 7.79 mmol) in THF (Volume: 15.06 ml) was added NaH (0.270 g, 6.76 mmol). The reaction was stirred at room temperature for 30 min, and then cooled to 0° C. To this mixture was added 3-bromo-4-chloropyridine (1 g, 5.20 mmol). The resulting mixture was refluxed for 16 hours, cooled to room temperature, and quenched with water. The mixture was evaporated to remove the THF and then extracted with DCM (2×). The combined organic layers were washed with water and brine, dried, and concentrated to give an oil. The oil was purified by silica gel chromatography (hexane: ethyl acetate 50:50) to afforded the title compound as a colorless oil. MS (ES): m/z=229 [M+H]+. Intermediate 66 was used in the synthesis of Example 255.

1. temperaturecooled to 0° C
2. temperatureThe resulting mixture was refluxed for 16 hours
3. temperaturecooled to room temperature
4. customquenched with water
5. customThe mixture was evaporated
6. customto remove the THF
7. extractionextracted with DCM (2×)
8. washThe combined organic layers were washed with water and brine
9. customdried
10. concentrationconcentrated
11. customto give an oil
12. customThe oil was purified by silica gel chromatography (hexane: ethyl acetate 50:50)

ORD record

ord-d36cac72c4664c84bfbd0d9face8fdf0

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08916553B2