Iodine → 4-Iodo-2-methoxynicotinaldehyde

Participants

Reaction Conditions

Reaction Steps

Methyllithium in diethyl ether (1.4 M, 23.5 mL, 33 mmol) was added to a solution of 2-methoxypyridine (1.93 mL, 18.3 mmol) in THF (120 mL) at −40° C. To this mixture was added diisopropylamine (0.128 mL, 0.9 mmol) upon which the mixture turned yellowish orange. After warming to 0° C. and stirring for 3 h, the mixture was cooled to −78° C. and N,N,N′-trimethyl-N′-formylethylenediamine (2.62 g, 20 mmol) was added slowly. The mixture was allowed to warm to −40° C. nBuLi in hexanes (1.6M, 22.9 mL, 36.6 mmol) was injected and the mixture was stirred for 3 h at −30° C. A solution of I2 (11.2 g, 44 mmol) in THF (70 mL) was then added dropwise through a dropping funnel at −78° C. with vigorous stirring. After 30 min, the resulting mixture was allowed to warm slowly to 0° C. (1 h), poured into 5% Na2SO3 (250 mL) and extracted with Et2O (3×150 mL) and the residue obtained after removal of the solvents was subjected to flash chromatography (hexanes/ethyl acetate 95:5) to provide 1b as a yellow oil (1.9 g, 40%). IR (CH2Cl2, NaCl, cm−1): 1703, 1551, 1462, 1368, 1298, 1265, 1017, 847, 736; 1H NMR (300 MHz, CDCl3) δ4.06 (s, 3H), 7.54 (d, J=5.3 Hz, 1H), 7.86 (d, J=5.3 Hz, 1H), 10.21 (s, 1H); 13C NMR (75 MHz, CDCl3) δ54.61, 108.75, 119.4, 130.52, 150.97, 164.44, 190.38; HRMS (EI): m/z calcd for C7H6INO2 (M+) 262.9443, found 262.9431; LRMS (EI) m/z 263 (M+, 100), 234 (80), 205 (30), 127 (30), 93 (28), 78 (72).

Provenance & Evidence