Methyl 4-formyl-2-hydroxybenzoate → 2-Hydroxy-4-(1-hydroxy-butyl)-benzoic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

4-Formyl-2-hydroxy-benzoic acid methyl ester (360 mg, 2 mmol) is dissolved in THF (anhydrous, 10 mL). The solution is cooled to −78° C. and stirred under nitrogen. To this solution is added n-propyl-magnesium chloride (2M in THF, 2 mL, 2 mmol) dropwise via syringe. The reaction mixture is stirred at −78° C. for 1 hour, then gradually warmed to room temperature over 1 hour after which point, the reaction is quenched by adding saturated aqueous ammonium chloride. The resulting mixture is extracted with EtOAc (3×15 mL). The combined organic phase is washed with saturated aqueous NaCl and dried over Na2SO4. After concentration, the crude product is purified with silica gel flash column chromatography (10-20% ethyl acetate in hexanes gradient) to afford 2-hydroxy-4-(1-hydroxy-butyl)-benzoic acid methyl ester as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 10.74 (s, 1H), 7.79 (d, 1H, J=8.4 Hz), 6.95 (d, 1H, J=1.2 Hz), 6.86 (dd, 1H, J=1.6, 8 Hz), 4.67 (t, 1H, J=6.8 Hz), 3.94 (s, 3H), 1.82 (br, 1H), 1.80-1.62 (m, 1H), 1.46-1.28 (m, 2H), 0.93 (t, 3H, J=7.2 Hz).

Provenance & Evidence