反应详情

To a stirred solution of racemic-(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxylic acid (48.2 mg, 0.103 mmol) in dichloromethane (8 ml) were added N,N-DIISOPROPYLETHYLAMINE (72.7 mg, 98.3 μl, 563 μmol, Eq: 6) and N,N,N′,N′-tetramethyl-O-(7-aza-benzotriazol-1-yl)uranium hexafluorophosphate (HATU) (64.2 mg, 0.169 mmol) followed by tert-butyl 4-amino-4-methylpiperidine-1-carboxylate (20.1 mg, 0.0938 mmol, Astatech). The reaction mixture was stirred from 2:00 PM for 2 hrs. The reaction mixture was diluted with CH2Cl2 (80 mL), washed with sat Na2CO3 (15 mL), water (2×15 mL) and evaporated. The crude material was purified by flash chromatography (silica gel, 4 g, 5% to 70% EtOAc in hexanes) to give rac-4-{[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-4-methyl-piperidine-1-carboxylic acid tert-butyl ester as a white solid. MS (ES+) m/z Calcd: [(M+H)+]: 663. found: 663.

1. washwashed with sat Na2CO3 (15 mL), water (2×15 mL)
2. customevaporated
3. customThe crude material was purified by flash chromatography (silica gel, 4 g, 5% to 70% EtOAc in hexanes)