Ethanethiol → {2-(4-Fluoro-phenyl)-6-hydroxy-benzo[b]thiophen-3-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

Participants

Reaction Steps

To a solution of the product from Example 17, Step 1 (83 mg, 0.32 mmol) and 4-(2-Piperidin-1-yl-ethoxy)-benzoyl chloride (1.39 mL, 0.39 mmol) in 3.3 mL of 1,2-dichloroethane was added, in two portions, aluminum trichloride (322 mg, 2.4 mmol) and the reaction was heated at reflux for 1 hr. At this time the coupling was complete and demethylation was carried out cooling the reaction to room temperature, adding ethanethiol (0.10 mL, 1.41 mmol) dropwise and stirring at room temperature for a further 1.5 hrs. The reaction was quenched with saturated sodium bicarbonate solution and extracted twice with methylene chloride. The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was chromatographed on silica gel using 1% MeOH:methylene chloride to 3% MeOH:methylene chloride as the gradient eluant to yield the title compound.

Provenance & Evidence