To a 100 mL three-neck flask was added Pd2(dba)3 (174 mg, 0.19 mmol, 0.03 equiv), 8-iodo-3-benzenesulfonylquinoline (2.5 g, 6.33 mmol), 1,1'-bis(diphenylphosphino)ferrocene (316 mg, 0.57 mmol), sodium tert-butoxide (851 mg, 8.86 mmol, 1.4 equivalents) and piperazine (2.72 g, 31.6 mmol, 5 equivalents). The flask was evacuated and displaced 4 times with nitrogen, then anhydrous 1,4-dioxane (17.5 mL, 7 vol) was added. The mixture was stirred and heated to 40 °C for 16 hours of reaction. After completion of the reaction, the dark solution was cooled to room temperature, dichloromethane (12.5 mL) was added and washed with deionized water (12.5 mL). The aqueous phase was extracted with dichloromethane and the combined organic phases were extracted with 5 M HCl (2 x 12.5 mL). The combined aqueous phases were washed with dichloromethane (2.5 mL) and transferred to a conical flask, dichloromethane (12.5 mL) was added and the flask was cooled in an ice water bath. An aqueous 1 M sodium hydroxide solution (13 mL) was added with stirring and the mixture was then stirred at room temperature until all solids were dissolved. The lower organic phase was separated, the aqueous phase was extracted with dichloromethane (7.5 mL), and the combined organic phases were concentrated under reduced pressure to about 5 mL. Crystallization was induced by the addition of iso-octane (2.5 mL) to the dark brown solution, and the mixture was stirred at room temperature for 5 minutes, followed by the slow addition of iso-octane (22.5 mL) over a 5 minute period. The mixture was aged at room temperature for 1.5 hours, then cooled in an ice water bath for 30 minutes, filtered and the filter cake was washed with isooctane (5 mL). The filter cake was dried under reduced pressure to afford the target product 3-(phenylsulfonyl)-8-(piperazin-1-yl)quinoline (1.67 g, 75% yield).1H NMR (CDCl3) δ: 1.6 (1H, bs), 3.18 (4H, m), 3.34 (4H, m), 7.27 (1H, m), 7.49-7.60 (5H, m), 8.01 (2H, dd), 8.75 (1H, d), 9.21 (1H, d).
