Iodine → 2,5-Dichloro-4-iodopyridine

Participants

Reaction Conditions

Reaction Steps

A solution of 2,5-dichloropyridine (10 g, 67.57 mmol) in THF (17 mL) was added dropwise to a stirred solution of n-BuLi in isohexane (33.8 mL, 67.57 mmol) and diisopropylamine (9.63 mL, 67.57 mmol) in THF (68.0 mL) cooled to −78° C., over a period of 1 hour under a nitrogen atmosphere. The resulting mixture was stirred at −78° C. for 30 minutes and then a solution of I2 (17.49 g, 68.92 mmol) in THF (17.0 mL) was added dropwise. The resulting solution was stirred at −78° C. for 1 hour and then quenched with water (75 mL) and allowed to warm to room temperature. The mixture was extracted with Et2O (3×100 mL) and the combined organic layers were dried over MgSO4, and then evaporated. The residue was triturated with CH2Cl2 to give a solid which was dried under vacuum to afford 2,5-dichloro-4-iodopyridine (9.72 g, 53% yield). The filtrate was evaporated and the residue purified by chromatography on silica, eluting with a gradient of 50-100% CH2Cl2 in isohexane. Fractions containing product were combined and evaporated and the residue triturated with MeOH to leave a second crop of 2,5-dichloro-4-iodopyridine (5.74 g, 31% yield); 1H NMR spectrum: (300 MHz, DMSO) δ 7.85 (1H, s), 8.34 (1H, s).

Provenance & Evidence