Synthesis
The general procedure for the synthesis of 4-bromo-6-chloro-2,3-dihydro-1H-inden-1-one using 3-(2-bromo-4-chlorophenyl)propionic acid as starting material was as follows: oxalyl chloride (3.6 mL) was added slowly and dropwise under stirring to a solution of 3-(2-bromo-4-chlorophenyl)propionic acid (4.4 g) in dichloromethane (40 mL). The reaction mixture was stirred continuously at 40 °C for 2 hours. Subsequently, aluminum trichloride (AlCl3, 2.7 g) was added to the reaction system and the mixture was heated to reflux and maintained for 1 hour. Upon completion of the reaction, the mixture was cooled to room temperature and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate (NaHCO3). The aqueous phase was extracted twice with ethyl acetate, all organic phases were combined and washed with brine. The organic layer was dried over anhydrous sodium sulfate (Na2SO4) and evaporated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography with the eluent cyclohexane/ethyl acetate (95:5→90:10) to afford the target compound 4-bromo-6-chloro-2,3-dihydro-1H-inden-1-one. Yield: 3.7 g; liquid chromatography (Method 1): retention time (tR) = 1.20 min; mass spectrometry (ESI+): m/z = 245 [M + H]+.
References
[1] Patent: WO2013/144098, 2013, A1. Location in patent: Page/Page column 123
[2] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 16, p. 3368 - 3372
