Imidazole → 3-Bromo-5-((triisopropylsilyloxy)methyl)pyridine

Participants

Reaction Steps

To a suspension of ethyl 5-bromonicotinate (10.0 g, 43.46 mmol) in anhydrous THF (20 mL) was added dropwise to a slurry of LiAlH4 (1.91 g, 47.81 mmol) in anhydrous THF (200 mL) under argon at −78° C. and the mixture was stirred for 1.5 h at the same temperature, then warmed to r.t. The reaction mixture was added 15 ml of aqueous HCl (1 M) slowly at −78° C., the mixture was then warmed to rt and added anhydrous Na2SO4, stirred for overnight. The resulting mixture was filtered through celite and the solvent was removed under reduced pressure to give crude (5-bromopyridin-3-yl)methanol, which was used in the next step without purification. To a solution of (5-bromopyridin-3-yl)methanol (10.6 g, 56.40 mmol) in DMF (30 mL) was added, under argon, imidazole (9.98 g, 146.5 mmol) followed by triisopropylsilyl chloride (TIPS—Cl) (15.53 mL, 73.29 mmol). After stirring for 24 h at room temperature the reaction mixture was evaporated to dryness. Purification by flash chromatography (silica gel, hexanes/EtOAc, 9:1) gave 3-bromo-5-((triisopropylsilyloxy)methyl)pyridine as a colourless oil (11.8 g, 81% overall). 1H NMR (CDCl3): d: 1.00-1.237 (m, 21H), 4.837 (s, 2H), 7.849 (s, 1H), 8.480 (s, 1H), 8.556 (s, 1H).

Provenance & Evidence