Triethylamine → (Z)-Methyl 3-(4-amino-3,5-dimethylphenyl)-2-(benzyloxycarbonyl)acrylate

Participants

Reaction Steps

A 2 L round bottom flask, was charged with 4-iodo-2,6-dimethylbenzenamine hydrochloride salt (55 g, 194 mmol), methyl 2-(benzyloxycarbonyl)acrylate (59.2 g, 252 mmol), tetrabutylammonium chloride (59.2 g, 213 mmol), palladium acetate (4.34 g, 19.4 mmol), and tetrahydrofuran (1.2 L, degassed by a flow of nitrogen for 30 min). The mixture was stirred to form a suspension and degassed by a flow of nitrogen for 30 min. Triethylamine (110 mL, 789 mmol) was then added and the resulting mixture was heated at reflux for 3 h. After cooling to room temperature, the reaction mixture was filtered through a pad of celite and washed twice with tetrahydrofuran (2×100 mL). The solvents were removed and the residue was dissolved in methylene chloride which was extracted with water (3×), brine (2×), dried over sodium sulfate and concentrated. Column chromatography on silica gel using 1:9 ethyl acetate/methylene chloride as eluent afforded a tan solid, which was recrystalized from methanol (210 mL) and water (100 mL). After filtration, the solid was washed with ice cold 1:1 methanol/water mixture and then dried under high vacuum overnight at room temperature to afford the title compound (58.0 g, 65%) as a light tan solid. NMR shows a 2.7:1 ratio of Z and E isomers which were not separated. 1H-NMR (DMSO-d6) δ 8.79 (s, 0.73 H), 8.51 (s, 0.27 H), 7.40-7.21 (m, 8H), 5.24 (s, 2H), 5.13 (s, 1.46 H), 5.00 (s, 0.54 H), 3.68 (s, 2.2 H), 3.61 (s, 0.8 H), 2.05 (s, 6H); 13C-NMR (DMSO-d6) δ 166.0, 154.7, 146.9, 137.2, 135.8, 130.9, 128.3, 127.7, 127.3, 120.3, 120.0, 119.4, 65.3, 51.7, 17.8.

Provenance & Evidence