反应详情

To a mixture of 1500 g of N-valeryl-5-iodoanthranilic acid in 14.5 L of N,N-dimethylformamide is added under nitrogen, 660 mL of triethylamine. The resulting solution is cooled to 0° to 5° C. and 432 mL of ethyl chloroformate added over 10 minutes at a rate to maintain the temperature below 10° C. The reaction mixture is heated to 35° to 50° C. for 2 hours until the evolution of carbon dioxide ceases. Analysis of a small aliquot of the reaction mixture by GC/MS indicates 93.7% (area %) conversion. The reaction mixture is cooled to 10°-15° C. and 5.0 L of concentrated ammonium hydroxide added over 10 minutes. The resulting slurry is then heated at 60°-70° C. for 14 hours. To the reaction mixture is added 10 L of water and the resulting slurry cooled to ambient temperature and filtered. The recovered solid is washed with 3 L of a 1:1 water-N,N-dimethylformamide solution followed by two 3 L water washes. The solid is dried at 50° C. to give 803 g (56.7%) of the desired product. The purity is 100% as analyzed by GC/MS.

1. additionis added under nitrogen
2. temperatureThe resulting solution is cooled to 0° to 5° C.
3. temperatureto maintain the temperature below 10° C
4. temperatureThe reaction mixture is cooled to 10°-15° C.
5. temperatureThe resulting slurry is then heated at 60°-70° C. for 14 hours
6. filtrationfiltered
7. washThe recovered solid is washed with 3 L of a 1:1 water-N,N-dimethylformamide solution
8. customThe solid is dried at 50° C.