Oxalyl chloride → 3-Bromo-4-fluorophenyl 6-methoxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl ketone

Beteiligte Stoffe

Reaktionsschritte

3-Bromo-4-fluorobenzoic acid (0.66 g; 3.0 mmol) and 1.57 mL (18.0 mmol) of oxalyl chloride in 10 mL of dichloromethane in a flask protected from moisture by a calcium chloride filled drying tube was stirred at room temperature for 24 h. The mixture was concentrated under reduced pressure to a white solid acid chloride. The crude acid chloride was dissolved in 50 mL of dichloroethane in an argon atmosphere, To this was added at 0° C. 6-methoxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophene (Example 1, Part B)(0.72 g; 2.0 mmol) and 1.6 g (12.0 mmol) of aluminum chloride. The mixture was stirred in the cold for 4 h, then poured into 200 mL of saturated aqueous sodium bicarbonate, and stirred for 1 h. Extraction was carried out with EtOAc (4×50 mL) and the combined organics were washed with brine and dried by passage through sodium sulfate. The mixture was subjected to flash chromatography on silica gel, eluting with a gradient of EtOAc(100-90%)/Et3N(0-5%)/MeOH(0-5%) to afford 3-bromo-4-fluorophenyl 6-methoxy-2-[4-[2-(1-pyrrolidinyl)-ethoxy]phenyl]benzo[b]thiophen-3-yl ketone contaminated with starting benzothiophene. This mixture was used without further purification.

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