反应详情

Bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (6.03 g, 12.9 mmol, 1.1 equiv.) and diisopropyl ethyl amine (3.19 g, 12.9 mmol, 1.1 equiv.) were added to a solution of quinoline-7-carboxylic acid (2.03 g, 11.75 mmol) in tetrahydrofuran (100 ml) and the resultant mixture stirred for 10 minutes. 4-Amino-2-chlorobenzoic acid methyl ester (2.40 g, 12.9 mmol, 1.1 equiv.) in tetrahydrofuran (20 ml) was added and the mixture refluxed for 16 hours. Additional Bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (1.10 g, 2.36 mmol, 0.2 equiv.) and diisopropyl ethyl amine (0.61 g, 4.7 mmol, 0.4 equiv.) were added and the mixture refluxed for a further 16 hours. The mixture was evaporated then dissolved in isopropanol (100 ml). Water (5 ml) and 60% aqueous perchloric acid (0.5 ml) were added and the mixture was refluxed for 24 hours. The mixture was filtered while hot then left to cool to room temperature whereupon a crystalline solid was formed. The solid was filtered and washed with cold isopropanol (20 ml) and dichloromethane (20 ml) to give 2-chloro-4-[(quinoline-7-carbonyl)-amino]-benzoic acid methyl ester, 1.42 g (35% yield), as a tan solid. LC @215 nm; Rt 1.11: 100%, m/z (ES+): 341 (M+H+.); δH (400 MHz; d6-DMSO) 10.96 (1H, br.s), 9.05 (1H, m), 8.73 (1H, s), 8.49 (1H, d), 8.18-8.10 (3H, m), 7.94 (2H, s), 7.68 (1H, dd), 3.86 (3H, s).

1. temperaturethe mixture refluxed for 16 hours
2. temperaturethe mixture refluxed for a further 16 hours
3. customThe mixture was evaporated
4. dissolutionthen dissolved in isopropanol (100 ml)
5. additionWater (5 ml) and 60% aqueous perchloric acid (0.5 ml) were added
6. temperaturethe mixture was refluxed for 24 hours
7. filtrationThe mixture was filtered while hot
8. waitthen left
9. customwas formed
10. filtrationThe solid was filtered
11. washwashed with cold isopropanol (20 ml) and dichloromethane (20 ml)