Chlorotrimethylsilane → 3-((4-(2-((1-(4-Methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)-methoxy)acetyl)piperazin-1-yl)methyl)benzonitrile hydrochloride

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Reaction Steps

N,N′-Carbonyldiimidazole (71 mg, 0.441 mmol) was added to a solution of 2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)acetic acid (150 mg, 0.420 mmol) in dichloromethane (7 ml), and the mixture was stirred for 1 h at room temperature. A solution of 3-(piperazin-1-ylmethyl)benzonitrile (84 mg, 0.420 mmol) in dichloromethane (3 ml) was then added, and the reaction mixture was stirred for 15 h at room temperature. Saturated sodium hydrogen carbonate solution (10 ml) was then added to the reaction mixture, and then the aqueous phase was extracted with dichloromethane (2×10 ml). The combined organic phases were extracted with saturated sodium chloride solution (10 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography using ethyl acetate/hexane/ammonia solution (25% aq.) (100:10:1). 3-((4-(2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)pyrrolidin-2-yl)methoxy)acetyl)piperazin-1-yl)methyl)benzonitrile (190 mg, 0.351 mmol) was dissolved in acetone/diethyl ether (1:1; 8 ml), and chlorotrimethylsilane (89 μl, 0.702 mmol) was added slowly. Diethyl ether (10 ml) was then added, and the mixture was stirred for 1 h at 0° C. The resulting precipitate was filtered off, dried with the exclusion of air and washed with diethyl ether.

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