反应详情

温度

22.5 °C

A mixture of 3-aminophthalic acid hydrochloride (200 g, 0.92 mol, from Prosynth Ltd., Suffolk, UK), 3-aminoglutarimide hydrochloride (159 g, 0.96 mol, from Evotec OAI, Hamburg, Germany), acetonitrile (2.0 L), and acetic acid (577 g, 9.6 mol, from Fisher Scientifc) was charged into a reaction vessel. After the mixture was stirred for 15 minutes, triethylamine (465.0 g, 4.6 mol, from Aldrich, Milwaukee, Wis.) was added dropwise over 30-35 minutes while the reaction temperature was maintained at 20-25° C. Next, the reaction mixture was stirred further for 10-15 minutes and then refluxed at about 85 to 87° C. for about 5 to 7 hours or until the in-process control, i.e., HPLC AP at 240 nm, indicates that <2% of the 3-aminophthalic acid remained in the reaction mixture. After the reaction mixture was cooled to about 20 to 25° C. over 1-2 hours, 1.0 L of water was charged over 15-30 minutes at about 20 to 25° C. The resulting mixture was stirred at about 15 to 20° C. for about 20 to 30 minutes to provide a yellow solid precipitate, which was filtered, washed with DI water (3×1.0 L) and acetonitrile (2×500 mL), and then dried at about 35 to 40° C in vacuo to a constant weight at 210.0 g (84 %).

1. additionwas charged into a reaction vessel
2. stirringNext, the reaction mixture was stirred further for 10-15 minutes
3. temperaturerefluxed at about 85 to 87° C. for about 5 to 7 hours
4. temperatureAfter the reaction mixture was cooled to about 20 to 25° C. over 1-2 hours
5. stirringThe resulting mixture was stirred at about 15 to 20° C. for about 20 to 30 minutes
6. customto provide a yellow solid precipitate, which
7. filtrationwas filtered
8. washwashed with DI water (3×1.0 L) and acetonitrile (2×500 mL)
9. customdried at about 35 to 40° C in vacuo to a constant weight at 210.0 g (84 %)