4-broMo-6-Methyl-2,3-dihydroinden-1-one

829-57-2

876-91-5

The general procedure for the synthesis of 4-bromo-6-methyl-1-indanone from 3-(2-bromo-4-methylphenyl)propionic acid was as follows: 3-(2-bromo-4-methylphenyl)propionic acid (2.4 g, 9.9 mmol) was dissolved in a solvent mixture of dichloromethane (12 mL) and N,N-dimethylformamide (0.1 mL, 1.3 mmol, 0.13 equiv). Oxalyl chloride (1.7 mL, 19.7 mmol, 2 eq.) was added slowly and dropwise over 7 min. The reaction mixture was stirred under nitrogen protection at room temperature for 1.5 h (LCMS monitoring showed complete consumption of starting material). The reaction solution was concentrated under reduced pressure to 1/3 of the original volume, followed by the addition of a suspension of pre-cooled aluminum chloride (1.7 g, 12.8 mmol, 1.3 eq.) in dichloromethane (10 mL) over 5 min, keeping the internal temperature below 5 °C. The reaction mixture was stirred at 3-5 °C for 20 min, and stirring was continued for 20 min after the ice bath was withdrawn (LCMS confirmed completion of the reaction). The reaction was quenched by the slow addition of pre-cooled aqueous 3M hydrochloric acid (20 mL) under cooling conditions. The reaction mixture was extracted with dichloromethane (3 x 25 mL). The organic phases were combined, washed with saturated saline (2 x 25 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residual solid was suspended with hexane and collected by filtration to give 2.0 g of white solid product (90% yield); the structure was confirmed to be correct by LCMS and NMR analysis. The filtrate was purified by silica gel column chromatography with petroleum ether/ethyl acetate as eluent (0 to 15% gradient) to give 0.1 g of product.LCMS analysis: retention time 2.75 min. Mass spectrum (m/z): [M + H]+ 225.0.