944086-09-3

51417-51-7

75-36-5

944086-09-3

A typical method for the synthesis of 1-(7-bromo-1H-indol-3-yl)ethanone from 7-bromoindole and acetyl chloride (Method 3, cf. Scheme 2, TP3) is as follows: first, 7-bromoindole (442 mg, 2.25 mmol) was dissolved in anhydrous dichloromethane (10 mL) at 0 °C, and diethylaluminum chloride (Et2AlCl, 3.4 mL. 1.0 M, 3.4 mmol). The reaction mixture was stirred at 0°C for 25 minutes. Subsequently, a dichloromethane (5 mL) solution of acetyl chloride (0.24 mL, 3.36 mmol) was added dropwise and stirring was continued at 0 °C until TLC showed complete conversion of 7-bromoindole (1-3 h). Upon completion of the reaction, saturated aqueous sodium bicarbonate solution (10 mL) was added slowly, the mixture was diluted with dichloromethane (60 mL) and carefully acidified to pH 4-5 with 2 M hydrochloric acid (~10 mL) to promote phase separation. The aqueous layer was extracted with dichloromethane and the combined organic layers were washed with saturated aqueous sodium bicarbonate and evaporated to dryness to give the acetylated crude product (496 mg, 93% yield). The crude product was dissolved in acetonitrile (10 mL), cesium carbonate (Cs2CO3, 1.55 g, 4.76 mmol) and 1-chloro-3-iodopropane (0.70 mL, 6.52 mmol) were added, and the mixture was stirred at 50 °C overnight. After completion of the reaction, the suspension was diluted with dichloromethane (70 mL), filtered and adsorbed onto diatomaceous earth. Purification by fast chromatography (eluent: heptane → heptane:ethyl acetate = 3:2) afforded the title product 1-(7-bromo-1-(3-chloropropyl)-1H-indol-3-yl)ethanone (611 mg, 86% overall yield in two steps). The structure of the product was confirmed by 1H NMR and 13C NMR.