Methanol → (2-Bromo-4-chloropyridin-3-yl)methanol

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-bromo-4-chloronicotinaldehyde 160a (20 g, 90.4 mmol), N,N-dimethylacetamide (15.6 g, 180.8 mmol) and methanol (8.8 g, 271 mmol) in 1,4-dioxane (150 mL) was added sodium borohydride (1.7 g, 45.2 mmol). See FIG. 5. The mixture was stirred at 20° C. for 10 min. TLC (petroleum ether:ethyl acetate=1:1) showed that the starting material was completely consumed. The mixture was quenched with saturated aqueous ammonium chloride solution (30 mL) and water (40 mL), and extracted with EtOAc (100 mL×2). The organic layers were washed with brine (100 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluting with petroleum ether:ethyl acetate from 50:1 to 1:1) to afford (2-bromo-4-chloropyridin-3-yl)methanol 160b (20 g, 95%) as a white solid.

Provenance & Evidence