Methanol → 2-Propenoic acid, 3-phenyl-, methyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of cinnamic acid (25 mmol) and concentrated H2SO4 (0.1 mL) in anhydrous MeOH (25 mL) was refluxed at 80° C. (bath temperature) for 16 h. After the excess MeOH was removed by a rotary evaporator, the residue was treated with H2O (50 mL), and the resulting mixture was extracted with EtOAc (3×50 mL). The combined extracts were washed with H2O (50 mL) and brine (50 mL), and dried (anhydrous Na2SO4). The solvent was evaporated to dryness, and the crude products were purified by flash silica gel chromatography (eluting with 10-60% hexane in EtOAc) to afford methyl cinnamate. To an ice-cold solution of methyl cinnamate described above (8 mmol) dissolved in anhydrous MeOH (10 mL) and THF (10 mL) was added hydroxylamine hydrochloride (1.67 g, 24 mmol, 3 equiv) followed by 25% sodium methoxide in methanol solution (8.4 mL, 36 mmol, 4.5 equiv). The reaction mixture was stirred under argon and at 0° C. for 2 h, then allowed to warm to ambient temperature with the stirring was continued overnight (16 h). The resulting yellow suspension was condensed to dryness with a rotary evaporator, and the residue was treated with 1N HCl aqueous solution (30 mL). The mixture was extracted with EtOAc (3×50 mL), and dried (anhydrous Na2SO4). Evaporation of the solvent afforded the crude products (480 mg), which was purified by flash silica gel chromatography (eluting with 5-15% MeOH in DCM) to afford the hydroxamate.

Provenance & Evidence