154257-85-9

14862-52-3

78191-00-1

154257-85-9

Example 26: Preparation of 1-(3-bromo-5-chlorophenyl)ethan-1-one (C148) (0740) (0741) 1,3-Dibromo-5-chlorobenzene (5.0 g, 18.5 mmol) was dissolved in diethyl ether (61.6 mL) and the solution was cooled to -78°C. After the compound was observed to precipitate from the solution, the mixture was removed from the cooling bath. When the temperature returned to a stir-able state, n-butyllithium (8.14 mL, 20.34 mmol) was added dropwise, followed by immersing the solution into the cooling bath again. The solution took on a bright yellow color and stirring of the mixture was continued for 30 minutes. At this point a slight yellow precipitate was seen to form. N-methoxy-N-methylacetamide (2.359 mL, 22.19 mmol) was added dropwise and the reaction mixture was stirred for 10 minutes before slowly warming to room temperature. The reaction mixture was quenched with 1N hydrochloric acid and subsequently extracted with ether. The organic extracts were combined, washed with brine, dried over sodium sulfate and concentrated. The resulting oil was purified by silica gel column chromatography using a gradient elution with a hexane solution of 0-15% acetone. Final isolation afforded 3-bromo-5-chloroacetophenone as a white solid (3.7 g, 86% yield): melting point 33-36 °C. The product was purified by silica gel chromatography. 1H NMR (300 MHz, CDCl3) δ 7.97-7.95 (m, 1H), 7.85 (dd, J = 1.5 Hz, 1H), 7.71 (t, J = 1.8 Hz, 1H), 2.59 (s, 3H); IR (thin film) 1687 cm-1; ESIMS m/z 233 ([M + H]+).