Diisopropylethylamine → HCID 72243912, compound

Participants

Reaction Steps

To a solution of rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (0.35 g, 0.749 mmol) in dichloromethane (25 ml) was added iPr2NEt (242 mg, 1.87 mmol) was added, followed by the addition of HATU (513 mg, 1.35 mmol) and 1-(4-aminophenyl)-2-(tert-butyldimethylsilyloxy)ethanone (398 mg, 1.5 mmol). The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was poured into H2O (50 mL) and extracted with dichloromethane (3×25 mL). The organic layers were combined, washed with H2O (1×50 mL), brine (50 mL), dried over MgSO4 and concentrated in vacuo. The residue was dissolved in THF (25 mL) and then an aqueous solution (1 N) of HCl (10 mL) was added. The reaction mixture was stirred at room temperature for 30 min. The mixture was concentrated in vacuo. The residue was poured into 20 mL saturated aqueous NaHCO3 and extracted with ethyl acetate (3×25 mL). The organic layers were combined, washed with H2O (25 mL), brine (25 mL), dried over MgSO4 and concentrated. The residue was purified by flash chromatography (silica gel, 40 g, 20% to 100% EtOAc in hexanes) to give rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid [4-(2-hydroxy-acetyl)-phenyl]-amide as a light yellow solid (0.17 g, 38%).

Provenance & Evidence