Hydrochloric Acid → Ethyl 3-(methoxycarbonyl)-β-oxobenzenepropanoate

Participants

Reaction Steps

Monomethyl isophathalate (2.0 g, 11.1 mmol) was dissolved in a 1:3 mixture of tetrahydrofuran and dichloromethane. Carbonyldiimidazole (1.89 g, 11.7 mmol) was added slowly. The mixture was then stirred under nitrogen for 1 hr at room temperature. In a separate flask, ethyl malonate, potassium salt (3.96 g, 23.3 mmol) was dissolved in acetonitrile and magnesium chloride (2.64 g, 27.8 mmol) and triethylamine (4.95 ml, 35.5 mmol) was added to result in a heterogeneous suspension, which was stirred at room temperature for 1 h. The two reaction mixtures were mixed, and the resulting suspension was stirred @80° C. for 8 hours. 100 ml of a 2N aqueous HCl solution was added to the reaction mixture, which was subsequently extracted with dichloromethane. The organic layer was washed with 2N HCl twice and twice with water, dried (MgSO4) and evaporated in vacuo to afford 4.0 g of an oil. Purification on silica gel using Biotage® eluting with 20% EtOAc in Hexanes, recovered 1.5 g of 6A as a clear oil. LC/MS: Retention Time=1.38 min (YMC S5 Turbopack 4.6×33mm, 2 min gradient; Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA) with a (M+H)+=251.13. 1H-NMR (Joel 500 Hz/ CDCl3) (1:2 mixture of enol and keto form) Keto: δ 1.17-1.21 (t, 3H, J=8.8 Hz), 3.89 (s, 3H), 3.96 (s, 2H), 4.12-4.18 (q, 2H, J=8.8 Hz) 5.67(s, 1H); 7.50-7.54 (t, 1H, J=9.3 Hz), 8.07-8.09 (d, 1H, J=9.9 Hz), 8.19-8.21 (d, 1H, J=9.9 Hz), 8.5 (d, 1H, J=2.2 Hz)

Provenance & Evidence