4-Fluorobenzoyl chloride → 4-Fluorophenyl 2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl ketone

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Reaction Steps

In a flame-dried, argon-filled flask were combined 1-[2-[4-(benzo[b]thiophen-2-yl)phenoxy]ethyl]pyrrolidine (Example 4, Part A) (3.54 g; 11.0 mmol) and 2.6 g (16.4 mmol) of 4-fluorobenzoyl chloride in 130 mL of dichloromethane. The mixture was cooled in an ice-water bath and protected from light with aluminum foil. Titanium tetrachloride (8.3 g; 43.8 mmol) was added dropwise. The mixture was stirred overnight while allowed to warm to room temperature. The mixture was poured into a rapidly stirred solution of 300 mL of saturated aqueous sodium bicarbonate. After stirring for 1 h, the mixture was transferred to a separatory funnel with 200 mL of water and extracted with dichloromethane (2×150 mL). The combined organics were dried by passage through sodium sulfate. The title compound was isolated as a yellow oil (4.4 g; 90% yield) by preparation HPLC using PrepLC, eluting with hexanes/THF/Et3N (75:20:5).

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