Formaldehyde → Ethyl 4-Methoxyatropate

Participants

Reaction Steps

To a solution of oxalic acid diethyl ester (18.8 ml, 0.14 mol) in tetrahydrofuran (10 ml) and benzene (10 ml) was added sodium hydride (80% oil suspension, 6.5 g, 0.22 mol) and then stirred for 10 minutes under argon atmosphere. A benzene solution (100 ml) of 2-(p-methoxyphenyl)acetic acid ethyl ester (1) (27.0 g, 0.14 mol) was added to the resulting solution and stirred for 3 days at room temperature. The reaction solution was quenched with aqueous 2N HCl solution and extracted with ether. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and then distilled under reduced pressure to remove the solvent. Thus, 48.0 g of the crude product was obtained. The obtained crude product was dissolved in water (150 ml) and 37% formalin (25 ml, 0.31 mol) was added dropwise thereto. To the reaction mixture was added dropwise aqueous potassium carbonate solution (24 g, 0.17 mol, 100 ml) and then stirred for 24 hours. The reaction solution was extracted with ether, and the organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent. The obtained crude product was then purified with silica gel column chromatography (ethyl acetate:hexane=1:5) to obtain 27.0 g (yield: 94%) of ethyl α-(4-methoxyphenyl)acrylate (2).

Provenance & Evidence