5-Bromo-2-iodopyridine → 5-Bromo-2-tert-butylpyridine

Temperature

-78 °C

To a THF (40 ml) suspension of copper cyanide (1.79 g, 20 mmol) which was dried under reduced pressure for 4 hours was added 1.0 M THF solution of tert-butylmagnesium chloride (40 ml, 40 mmol) dropwise at −78° C. over 30 minutes and the mixture was stirred for 1 hour at −78° C. 5-Bromo-2-iodopyridine (2.83 g, 10 mmol) was added at −78° C. and the mixture was stirred for 1 hour at −78° C., followed by additional stirring for 16 hours at room temperature. Then, the reaction was quenched with 25% aqueous ammonia solution (40 ml) and the precipitates were removed by filtration and washed with EtOAc. The filtrate and washings were combined and concentrated in vacuo. Then, filtration, evaporation, and purification by silica gel column chromatography, eluting with hexane/EtOAc (20:1), gave the title compound (1.07 g, 50% yield) as a colorless oil.

1. customwas dried under reduced pressure for 4 hours
2. stirringthe mixture was stirred for 1 hour at −78° C.
3. stirringby additional stirring for 16 hours at room temperature
4. customThen, the reaction was quenched with 25% aqueous ammonia solution (40 ml)
5. customthe precipitates were removed by filtration
6. washwashed with EtOAc
7. concentrationconcentrated in vacuo
8. filtrationThen, filtration, evaporation, and purification by silica gel column chromatography
9. washeluting with hexane/EtOAc (20:1)

ORD record

ord-29755ff8f9754f60995e931b082d39a6

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07915448B2