Toluene (111 ml) and N-methylmorpholine (3.85 ml, 35.0 mmol) were added to N-[(4-dimethylaminophenyl)acetyl]-D-proline (8.56 g, 31.0 mmol). Ethyl chloroformate (3.26 ml, 34.1 mmol) was added to the obtained mixture, and they were stirred for 2 hours. 2-(2-Bromo-4-chlorobenzyloxy)aniline hydrochloride (10.8 g, 31.0 mmol) and N-methylmorpholine (4.09 ml, 37.2 mmol) were added thereto and they were stirred at room temperature overnight. Water (40 ml) was added to the reaction mixture. The organic layer was washed with water (40 ml) and then dried over sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to the silica gel column chromatography. After the elution with methylene chloride and methanol (30:1), suitable fractions were collected and the solvent was evaporated under reduced pressure to obtain the title compound in the form of a yellow solid (16.3 g, 92%).
