Diisopropylethylamine → (1,1-Dioxido-4-thiomorpholinyl)[5-[[1-(1-methylethyl)-4-piperidinyl]oxy]-1-(2,2,2-trifluoroethyl)-1H-indol-2-yl]methanone

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Reaction Steps

A mixture of 5-(1-isopropyl-piperidin-4-yloxy)-1-(2,2,2-trifluoro-ethyl)-1H-indole-2-carboxylic acid, hydrochloric salt with one equivalent of lithium chloride (650 mg, 1.0 eq.), 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethylurunium tetrafluoroborate (563 mg, 1.2 eq.), thiomorpholine-1,1-dioxide (purchased at Syntec, ref. M1201) and diisopropylethylamine (1.22 mL, 5 eq.) in dimethylformamide was stirred at room temperature for 24 h and then partitioned between an aqueous solution of sodium hydrogenocarbonate and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water and brine, dried over sodium sulfate, filtered, evaporated in vacuo and purified on silica eluting with dichloromethane/methanol/ammoniac. One fraction was isolated and dried in vacuo, to yield 468 mg (66%) of the desired product as off-white solid. MS (m/e): 502.5 (MH+, 100%).

Provenance & Evidence