Cyclobutanone → 1-((((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)amino)cyclobutanecarbonitrile

Participants

Reaction Steps

A 5-mL vial was charged with 2-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (0.202 g, 0.448 mmol, Example 192, Step 2), cyclobutanone (0.0364 g, 0.519 mmol, Alfa Aesar, Ward Hill, Mass.) and 1,2-dichloroethane (2.5 mL). The solution was stirred at room temperature for 20 min then trimethylsilanecarbonitrile (0.120 mL, 0.959 mmol, Sigma-Aldrich, St. Louis, Mo.) was added. After stirring at room temperature for 12 h, the material was purified by column chromatography (10 g of silica, 20 to 70% EtOAc in hexanes) to afford 1-((((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)amino)cyclobutanecarbonitrile (0.198 g) as a white solid.

Provenance & Evidence