反应详情

To a solution of [1-(3-chloro-2-fluoro-phenyl)-meth-(E)-ylidene]-methyl-amine (1.72 g, 10.00 mmol) and (Z)-2-(4-chloro-2-fluoro-phenyl)-5,5-dimethyl-hex-2-enenitrile (2.52 g, 10.00 mmol) in DMSO (10 mL) was added KOH powder (1.12 g, 20.00 mmol) in one portion. The mixture was stirred at rt overnight. The reaction mixture was diluted with water and extracted with EtOAc three times (3×50 mL). The combined organic layers were washed with water and brine and dried over Na2SO4, and concentrated. The residue was purified by flash column (SiO2, 1%-15% of EtOAc in hexanes) after concentration to give rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)-pyrrolidine-3-carbonitrile (0.86 g, 20.3%; HRMS (ES+) m/z Calcd for C22H22Cl2F2N2+H [(M+H)+]: 423.1201, found: 423.1199) and rac (3S,4S,5S)-5-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-4-(2,2-dimethyl-propyl)pyrrolidine-3-carbonitrile (0.66 g, 15.6%); HRMS (ES+) m/z Calcd for C22H22Cl2F2N2+H [(M+H)+]: 423.1201. found: 423.1202.

1. extractionextracted with EtOAc three times (3×50 mL)
2. washThe combined organic layers were washed with water and brine
3. dry with materialdried over Na2SO4
4. concentrationconcentrated
5. customThe residue was purified by flash column (SiO2, 1%-15% of EtOAc in hexanes)
6. concentrationafter concentration