反应详情

To a solution of (2′-ethylaminomethyl-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid ethyl ester (0.170 g, 0.43 mmol) in CH2Cl2 (2 mL) at 0° C. was added diisopropylethylamine (0.19 mL, 1.08 mmol), followed by phosgene (20% in toluene; 0.34 mL, 0.64 mmol), and the mixture was stirred for 1.5 hours. 3,5-Dichlorobenzylamine (0.091 g, 0.52 mmol) was added, followed by triethylamine (0.12 mL, 0.86 mmol), and the reaction was warmed to room temperature and stirred for 45 minutes. Additional triethylamine (0.12 mL, 0.86 mmol) was added, and the reaction was stirred for 1.5 hours. Another portion of triethylamine (0.25 mL, 17.9 mmol) was added, and the reaction was stirred overnight at room temperature. The mixture was worked up with CH2Cl2 and H2O, and the aqueous layer was extracted twice with CH2Cl2. The combined organic layers were dried and concentrated, and the residue was purified by silica gel chromatography (0-50% EtOAc in hexanes) to give the title compound.

1. stirringstirred for 45 minutes
2. stirringthe reaction was stirred for 1.5 hours
3. stirringthe reaction was stirred overnight at room temperature
4. extractionthe aqueous layer was extracted twice with CH2Cl2
5. customThe combined organic layers were dried
6. concentrationconcentrated
7. customthe residue was purified by silica gel chromatography (0-50% EtOAc in hexanes)