1,1'-Carbonyldiimidazole → Isatoic Anhydride

Participants

Reaction Steps

There was suspended, in 7.6 mL of N,N-dimethylformamide, 1.67 g of 1,1′-carbonyl-diimidazole (CDI) and the suspension was cooled to 5° C. To this slurry, there was added 2.0 g of 2-amino-5-(N-formyl-N-methylamino-methyl)-benzoic acid to thus carry out a reaction for forming an isatoic anhydride derivative at 5° C. After the confirmation of the completion of the reaction by HPLC, 3.80 g of 4-amino-Nα-(2,6-dichlorobenzoyl)-L-phenylalanine isopropyl ester was added to the reaction system to thus carry out amidation at 60° C. overnight. After the confirmation of the completion of the reaction by HPLC, the reaction system was cooled to a temperature ranging from 25 to 50° C. followed by the addition of 3 mL of water. This solution was slowly dropwise added to another egg plant-shaped flask to which 29 mL of water had previously been added to thus form a solid material and then the separated solid was isolated through filtration under reduced pressure. After washing the solid with 20 mL of water, it was dried under reduced pressure to thus give 5.50 g of a crude product of the intended compound. To this crude product, there was added 5.5 mL of acetonitrile to obtain a uniform dispersion, 137.5 mL of 2-propanol and seed crystals were added thereto to precipitate a solid material and the slurry was stirred at 20° C. for 2 hours. The solid thus separated was isolated through filtration under reduced pressure, washed with 20 mL of 2-propanol and then dried under reduced pressure to thus give 2.60 g of the intended product as a white crystalline solid.

Provenance & Evidence