These common heterocyclic compound, 391211-97-5, name is 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Recommanded Product: 391211-97-5
To a flask containing 3, 4-difluoro-2- (2-fluoro-4-iodo-phenylamino)-benzoic acid (2.6 Kg, 6.6 mol) and N, N’-carbonyldiimidazole (1.1 Kg, 6.8 mol) under nitrogen atmosphere, was added 12 L of dry acetonitrile. After stirring at 22 5C for about 90 minutes, a solution of (R)-O- (2, 2-dimethyl- [1, 3] dioxolan-4-ylmethyl)-hydroxylamine in toluene was added (8.5 L total volume, about 8 moles of amine). The solution was stirred for at least 6 hours at 22 5 C. Aqueous hydrochloric acid (9 L, 1.5 molar) was added, and after stirring for about 5 minutes, the layers were separated. Aqueous hydrochloric acid (9 L, 1.5 molar) was added to the remaining top layer, and after stirring for about 20 hours, the layers were separated. The remaining top layer was concentrated by vacuum distillation, and then diluted with 15 L toluene and 2 L ethanol. The mixture was warmed to 35-45C and diluted with 20 L warm water, then cooled to 0-5C. The product was collected by filtration and washed with 2 L toluene. The product was recrystallized by dissolving in 12 L toluene and 2 L ethanol (50 5 C), adding 10 L water and cooling to 0-5C. After collecting the product by filtration and washing with toluene, the product was dried in a vacuum oven resulting in 2.6 Kg of N-[(R)- 2,3-Dihydroxypropoxy]-3, 4-difluoro-2- (2-fluoro-4-iodo-phenylamino)-benzamide. 2.4 Kg of the above compound as a mixture of different crystalline forms was stirred in a mixture of 10 L water and 1 L ethanol at 35+ 5C for 20-30 hours, then cooled to 25+ 5C. The product was collected by filtration and washed with 1 L of water, then dried in a vacuum oven at 65C. This resulted in 2.3 Kg of material which was greater than 90% form IV. Note: DSC analysis shows an onset of melting at 110C with only a small amount of the peak with an onset of melting at 117C.
The synthetic route of 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid has been constantly updated, and we look forward to future research findings.
Reference:
Patent; WARNER-LAMBERT COMPANY LLC; WO2005/46665; (2005); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com