Diethyl methylmalonate → 3-(2,5-Dibromophenyl)-2-methylpropanoic acid

참여 물질

반응 단계

In a three-necked round-bottom 1000 ml flask equipped with a reflux condenser, dropping funnel with pressure-equalizing, and magnetic stirring bar 6.10 g (0.27 mol) of sodium metal were dissolved in 150 ml of dry ethanol. To the resulting solution 45.5 g (0.26 mol) of diethylmethylmalonate in 50 ml of dry ethanol were added dropwise within 10 min. This mixture was stirred for 15 min; then 84.3 g (0.26 mol) of 3,6-dibromobenzylbromide were added by vigorous stirring at a rate that allowed the reaction mixture to maintain a gentle reflux. Additionally, this mixture was refluxed for 4 h and, then, cooled to room temperature. A solution of 52.1 g of KOH in 140 ml of water was added. This mixture was refluxed for 3 h to saponificate the ester formed. Ethanol and water were distilled off. To the residue 200 ml of water and, then, 12 M HCl (to pH 1) were added. The substituted methylmalonic acid precipitated was separated, washed with 3×100 ml of cold water and dried overnight on a watch glass. Crude 3-(2,5-dibromophenyl)-2-methylpropanoic acid was obtained after decarboxylation of this substituted methylmalonic acid by heating it for 2 h at 160° C. This product was used without further purification. A mixture of this acid, 70 ml of SOCl2, and 100 ml of CH2Cl2 was stirred for 3 h at reflux. Thionyl chloride and CH2Cl2 were distilled off. The residue was dried in vacuum and, then, dissolved in 95 ml of CH2Cl2. To a suspension of 47.0 g (0.35 mol) of AlCl3 in 470 ml of CH2Cl2 the above-obtained solution of 3-(2,5-dibromophenyl)-2-methylpropanoyl chloride was added dropwise by vigorous stirring for 1 h at −20° C. This mixture was refluxed for 3 h, cooled to ambient temperature, and, then, poured on 500 cm3 of ice. The organic layer was separated. The aqueous layer was extracted with 3×200 ml of methyl-tert-butyl ether. The combined organic fractions were dried over K2CO3 and evaporated to dryness. The crude 4,7-dibromo-2-methyl-1-indanone was purified by flash chromatography on Silica Gel 60 (40-63 μm, d 50 mm, h 250 mm; eluent:hexanes/methyl-tert-butyl ether (1:1, vol.)). Yield 54.1 g (70%).

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