Hydrochloric Acid → 2-Chloro-5-iodo-4-methylpyridine

Participants

Reaction Steps

To a stirred solution of concentrated hydrochloride acid (233 mL) at 0° C. was added 5-iodo-4-methyl-pyridin-2-ylamine (25 g, 107 mmol, 1 eq) followed by addition of pre-dissolved sodium nitrite (29.5 g, 427 mmol, 4 eq) in water (100 mL) in drop wise manner over period of 30 minutes. Resulting reaction mixture was stirred at room temperature for 16 hours. After complete consumption of starting material, reaction mixture was cooled to 0° C. and pH was adjusted to 12 by saturated aqueous sodium hydroxide solution, extracted with DCM (3×200 mL). Combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to get brown oil (23 g, crude). Crude was purified by column chromatography using silica gel (100-200 mesh). Desired compound was eluted at 4% ethyl acetate in hexane to get title compound as brown oil (8 g, 30%). 1H NMR (400 MHz, CDCl3) δ: 2.38 (s, 3H), 7.21 (s, 1H), 8.59 (s, 1H). LC-MS (m/z): 253.7 (M+H).

Provenance & Evidence