Dimethylformamide → (6-Bromopyridin-2-yl)methanol

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Reaction Steps

Add n-butyl lithium (16.2 mL, 2.5 M in hexanes, 40.5 mmol) dropwise to a solution of 2,6-dibromopyridine (8.00 g, 33.8 mmol) in tetrahydrofuran (100 mL) at −78° C. Stir 30 minutes then add dimethylformamide (12.3 g, 169 mmol) via syringe. Allow solution to warm to ambient temperature then pour it into a solution of sodium borohydride (17.85 g, 338 mmol) in ethanol (50 mL) at −10° C. After 10 minutes, remove the cooling bath. After 1 hour at ambient temperature, add water and 1N hydrochloric acid (gas evolution), then add saturated sodium bicarbonate solution until the mixture is neutralized. Extract the aqueous phase with ethyl acetate, dry over sodium sulfate, filter and concentrate under reduced pressure. Dissolve the residue in diethyl ether and add an excess of hydrogen chloride (2N in diethyl ether). Decant the organic phase and add saturated sodium bicarbonate solution to the residue. Extract with ethyl acetate (3×), dry over sodium sulfate, filter and concentrate under reduced pressure to afford the title compound as a brown oil (2.73 g, 14.5 mmol): MS (m/z): 189 (M+1).

Provenance & Evidence