反应详情

温度

0 °C

A 5-mL vial was charged with 2-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (0.0521 g, 0.116 mmol, Example 192, Step 2), acetone (10 μL, 0.14 mmol) and EtOH (1 mL). The reaction mixture was cooled to 0° C. and stirred for 35 min. Trimethylsilyl cyanide (46.3 μL, 0.348 mmol, Sigma-Aldrich, St. Louis, Mo.) was added drop wise at 0° C. The mixture was slowly allowed to warm up to room temperature and stirred for 12 h. The solvent was removed and the remaining white residue was dissolved into EtOAc and passed through a pad of silica gel rinsing with EtOAc as eluent. The solvent was removed and the crude product was purified by column chromatography (10 g of silica gel, 50 to 100% EtOAc in hexanes) to afford 2-methyl-2-((((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)amino)propanenitrile (0.0312 g) as an off-white solid.

1. temperatureto warm up to room temperature
2. stirringstirred for 12 h
3. customThe solvent was removed
4. dissolutionthe remaining white residue was dissolved into EtOAc
5. customThe solvent was removed
6. customthe crude product was purified by column chromatography (10 g of silica gel, 50 to 100% EtOAc in hexanes)