Dimethylformamide → 6-Methoxypyridine-3-carbaldehyde

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Reaction Steps

N-Butyl lithium (50 mL, 2.5M in hexane) was added drop wise to a solution of 5-Bromo-2-methoxy-pyridine (22.4 g, 119.1 mMol) in dry tetrahydrofuran (240 mL) at −78 degrees. After complete addition the solution was stirred at −78 for an additional ninety minutes at which time dimethylformamide (18.5 mL, 238.3 mMol) was added drop wise and the solution stirred for ninety more minutes at −78 and then allowed to warm to room temperature. The mixture was then poured into saturated sodium bicarbonate solution (1000 mL) and extracted with diethyl ether (3×250mL). The combined organics were dried with magnesium sulfate, filtered, and concentrated to dryness to yield 15.4 g (94% yield) of 6-Methoxy-pyridine-3-carbaldehyde as a pale yellow solid. 1H NMR (DMSO-d6): δ=9.97 (s,1H), 8.77 (m, 1H), 8.12 (dd, 1H, J=8.6, 2.3 Hz), 6.99 (d, 1H, J=8.7 Hz), 3.97 (s, 3H). LC/MS (Method A), rt=0.25 mins., purity=92.8%, calculated mass=137, [M+H]+=138. HPLC (Method C): rt=4.9 mins., purity=95.9% @ 210-370 nm and 98.7% @ 256 nm.

Provenance & Evidence