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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence