Iodine → 4-Iodo-2-methoxynicotinaldehyde

Participants

Reaction Conditions

Reaction Steps

A −78° C. solution of 2-methoxypyridine (40 g, 0.37 mol) in THF (1 L) was treated with t-BuLi (163 mL, 0.41 mol), stirred at −78° C. for 0.5 h, treated with N-(2-dimethylaminoethyl)-N-methylformamidine (52.9 g, 0.41 mol) over 10 min, stirred at −78° C. for another 0.5 h, then warmed to −20° C. for 45 minutes. The mixture was cooled to −40° C., treated with n-BuLi (289 mL, 0.46 mol), stirred at −40° C. for 1.5 h, then cooled to −78° C. The cold mixture was added via syringe to a solution of I2 (187.8 g, 0.74 mol) in THF at −78° C., stirred at −78° C. for 0.5 h, then warmed to 0° C. The mixture was quenched with satd. NaS2O3, the organic layer washed with brine, dried over Na2SO4, concentrated under reduce pressure, and purified by chromatography. The resulting solid was washed with pet ether to afford 4-iodo-2-methoxynicotinaldehyde (22 g, 23%). 1H NMR (400 MHz, CDCl3): δ 10.20 (s, 1H), 7.84 (d, J=5.6 Hz, 1H), 7.53 (d, J=5.2 Hz, 1H), 3.99 (s, 3H).

Provenance & Evidence