反应详情

To a stirred solution of bromo-acetyl chloride (0.80 g, 4 mmol) in CH2Cl2 (5 ml) at 0° C. was added over 1 hour a solution of rac-2-(3,5-bis-trifluoromethyl-phenyl)-N-[(3S,4R)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-N-methyl-isobutyramide (pyrrolidine interm. VII-4 described herein above, 0.94 g, 1.97 mmol) and ethyl-diisopropyl-amine (0.37 ml, 2.17 mmol) in CH2Cl2 (10 mL). The reaction was stirred over night, quenched by addition of an aqueous solution of NaHCO3, and the product extracted with CH2Cl2. Purification by flash chromatography (SiO2, EtOAc/Hx 1:1) yielded 0.83 g (70%) of rac-2-(3,5-bis-trifluoromethyl-phenyl)-N-[(3S,4R)-1-(2-bromo-acetyl)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-N-methyl-isobutyramide as a white foam.

1. customquenched by addition of an aqueous solution of NaHCO3
2. extractionthe product extracted with CH2Cl2
3. customPurification by flash chromatography (SiO2, EtOAc/Hx 1:1)