2,5-Dibromopyridine → 1206912-74-4

Participants

Reaction Steps

A solution of 2,5-dibromopyridine (1 g, 4.22 mmol) in anhydrous toluene (15 mL) was cooled to −78° C. with stirring under nitrogen. n-Butyllithium (2.5M solution in hexanes, 1.7 mL) was added dropwise over 10 minutes. The reaction mixture was stirred at −78° C. for 1 h, then tetrahydro-4H-pyran-4-one (0.43 mL, 4.66 mmol) was added slowly. The reaction mixture was allowed to warm to ambient temperature, then stirred for 2 h. The reaction mixture was quenched with saturated aqueous ammonium chloride solution (20 mL) and extracted into ethyl acetate (2×20 mL). The combined organic phases were dried over sodium sulfate and concentrated under vacuum. The resulting pale brown oil (983 mg) was purified by chromatography on silica (Biotage, 25 g cartridge), eluting with 0-60% ethyl acetate in heptanes. The resulting yellow solid (578 mg) was re-purified by chromatography on silica (Biotage, 10 g cartridge), eluting with 0-50% ethyl acetate in heptanes, to afford the title compound (363 mg, 32.3%) as a yellow solid. δH (500 MHz, DMSO-d6) 8.60 (d, J 2.2 Hz, 1H), 7.86 (dd, J 8.4, 2.3 Hz, 1H), 7.31 (d, J 8.4 Hz, 1H), 4.67 (s, 1H), 3.98 (td, J 11.7, 1.8 Hz, 2H), 3.94-3.89 (m, 2H), 2.11 (td, J 12.7, 5.5 Hz, 2H), 1.56 (d, J 12.2 Hz, 2H). Method B HPLC-MS: MH+ m/z 258/260, RT 1.44 minutes.

Provenance & Evidence