Hydrochloric Acid → 2-Chloro-4-iodopyridine-3-carbaldehyde

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Reaction Steps

A mixture of 2-chloro-3-iodopyridine (5.0 g, 21 mmol) in dry THF (30 mL) was slowly added to a cold (−78° C.) solution of lithium diisopropylamide (15 mL, 30 mmol) in dry THF (50 mL). The resulting mixture was stirred for 3 h at this temperature. Ethyl formate (4.0 g, 54 mmol) was then added. Stirring was continued for 1.5 h at the same temperature. Water (10 mL) was added to quench the reaction, and then the resulting mixture was warmed to room temperature. 2M HCl (50 mL) was added and then the THF was removed under reduced pressure. The aqueous residue was extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified on silica gel (diethyl ether:petroleum ether=1:4) to give the desired product 2-chloro-4-iodonicotinaldehyde as a yellow solid (3.0 g, 54% yield). 1H NMR (500 MHz, CDCl3): δ 10.22 (s, 1H), 8.09 (d, J=5.0 Hz, 1H), 7.95 (d, J=5.0 Hz, 1H).

Provenance & Evidence