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

Temperature

-78 °C

To a suspension of copper cyanide (1.791 g, 20 mmol) in dry tetrahydrofuran (40 mL) at −78° C. under nitrogen was added dropwise a solution of tert-butylmagnesium chloride in tetrahydrofuran (1.0 M, 40 mL, 40 mmol) over 20 minutes. A solution of 5-bromo-2-iodopyridine (5.68 g, 20 mmol) in dry tetrahydrofuran (20 mL) was then added via cannula and the reaction mixture stirred at −78° C. for 1 hour then allowed to warm slowly to room temperature. The reaction was quenched by the addition of 25% aqueous ammonium hydroxide solution (28-30%, 100 mL) and the mixture partitioned between ethyl acetate (500 mL) and 25% aqueous ammonium hydroxide solution (28-30%, 400 mL). The organic phase was separated, washed with water (400 mL) and saturated brine (100 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give a brown oil. The crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 10% ethyl acetate in hexanes to give 5-bromo-2-(tert-butyl)pyridine (1.6186 g, 38% yield) as a colorless oil.

1. temperatureto warm slowly to room temperature
2. customThe reaction was quenched by the addition of 25% aqueous ammonium hydroxide solution (28-30%, 100 mL)
3. customthe mixture partitioned between ethyl acetate (500 mL) and 25% aqueous ammonium hydroxide solution (28-30%, 400 mL)
4. customThe organic phase was separated
5. washwashed with water (400 mL) and saturated brine (100 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto give a brown oil
10. customThe crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 10% ethyl acetate in hexanes

ORD record

ord-cc7fdce493fc4890a988da0751504f59

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09409893B2