Methyl Acrylate → 2-[Hydroxy-(6-methyl-pyridin-3-yl)-methyl]-acrylic acid methyl ester

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Reaction Steps

A mixture of 6-methylpyridine-3-carboxaldehyde, 97% (500 mg, 4.0 mmol, 1 eq), DABCO (458 mg, 1 eq) and methyl acrylate (1.80 ml, 5 eq) in a 1,4-dioxane (20 ml)/water (20 ml) solvent mixture was stirred at room temperature for 4 days. The resulting mixture was poured in 150 ml of brine and the organics were extracted with DCM (3×300 ml). The gathered DCM layers were dried, solvent was evaporated and the obtained crude was purified by chromatography on Biotage SP1 purification device using 25 g normal phase silica SNAP column and DCM/MeOH solvent system (gradient 1-6% of MeOH in 20 CV). Solvent from gathered fractions of appropriate composition was evaporated and the resulting crude was triturated with cyclohexane to obtain 2-[hydroxy-(6-methyl-pyridin-3-yl)-methyl]-acrylic acid methyl ester in form of white powder (375 mg, yield=43.8%, purity=95%). MS: [M+H]+=208.17 1H NMR (300 MHz; CDCl3) δ/ppm 2.55 (s, 3H), 3.11 (d, J=5.86 Hz, 1H), 3.74 (s, 3H), 5.58 (d, J=5.58 Hz, 1H), 5.87 (s, 1H), 6.38 (s, 1H), 7.15 (d, J=8.13 Hz, 1H), 7.61 (dd, J=8.13 Hz, J=2.45 Hz, 1H), 8.48 (d, J=2.45 Hz, 1H)

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