Hydrochloric Acid → Ethyl 3-(5-bromo-2,4-dimethoxyphenyl)-3-oxopropionate

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, to a suspension of anhydrous magnesium chloride (36.5 g) and ethyl acetate (200 mL) was slowly added dropwise tetrahydrofuran (55.2 g). After completion of the dropwise addition, the mixture was stirred at 75° C. for 2 hr to dissolve anhydrous magnesium chloride. The solution was added dropwise to an ice-cold suspension of potassium ethylmalonate (52.1 g) and triethylamine (46.5 g) in ethyl acetate (200 mL). After the dropwise addition, the suspension was warmed to 70° C. To the suspension was slowly added dropwise at 70° C. a suspension of 5-bromo-2,4-dimethoxybenzoic acid chloride obtained in Step 2 of Example 1 in tetrahydrofuran. After completion of the dropwise addition, the mixture was stirred at 70° C. for 0.5 hr, and the completion of the reaction was confirmed by HPLC. 2N Hydrochloric acid (240 mL) was added dropwise to the reaction mixture under ice-cooling, and the mixture was stirred at room temperature for 1 hr. The organic layer was separated, and washed successively with water (200 mL), twice with 5% sodium hydrogencarbonate (200 mL), and water (200 mL). After washing, the solvent was evaporated under reduced pressure, toluene (200 mL) was added to the concentrated residue, and the mixture was concentrated again under reduced pressure. The obtained ethyl 3-(5-bromo-2,4-dimethoxyphenyl)-3-oxopropionate (52.8 g) as a white solid was directly used in the next step.

Provenance & Evidence