(3,5-Dichloropyridin-4-yl)methanol → (3-Bromo-5-chloropyridin-4-yl)methanol

Participants

Reaction Steps

A solution of LDA (7.94 mL, 1.8 M in THF/heptane/ethylbenzene, 14.3 mmol) in anhydrous THF (30 mL) at −78° C. under Ar was treated dropwise with a solution of 3-bromo-5-chloro-pyridine (2.5 g, 13.0 mmol) in anhydrous THF (30 mL) The solution was stirred at −78° C. for 30 min, then a solution of ethyl formate (10.46 mL, 130 mmol) in anhydrous THF (30 mL) was added dropwise. The resulting solution was stirred at −78° C. for 1.5 h and then treated with saturated NaHCO3 with vigorous stirring. The quenched mixture was extracted with EA (2×25 mL) and the combined organic extracts were washed with saturated NaHCO3 (15 mL) and dried over Na2SO4. The residue was purified by flash chromatography on silica gel with EA/hexane to provide 3-bromo-5-chloro-pyridine-4-carbaldehyde as a yellow solid. Reduction of the aldehyde according to the synthesis of (3,5-dichloro-pyridin-4-yl)-methanol yielded the title compound. MS (m/z): 224.0 [M+H+].

Provenance & Evidence