Synthesis
General procedure for the synthesis of 4,5-difluorophthalimide from 2-nitro-4,5-difluoroaniline: 4,5-difluoro-2-nitroaniline (10 g, 57 mmol) was co-suspended in methanol (150 mL) with 10% palladium carbon catalyst (2.0 g, 1.9 mmol). The reaction system was transferred to a hydrogenation unit and the catalytic hydrogenation reaction was carried out under 50 psi hydrogen pressure. After 3 hours of reaction, the catalyst was removed by filtration through a diatomaceous earth pad and the filtrate was concentrated under reduced pressure to give a solid product. The resulting solid was dried under vacuum at room temperature overnight to obtain white crystalline 4,5-difluorophthalimide (8.05 g, 98% yield).
References
[1] Journal of Medicinal Chemistry, 1993, vol. 36, # 3, p. 331 - 342
[2] Patent: US2005/43292, 2005, A1. Location in patent: Page/Page column 14
[3] Patent: EP2766359, 2016, B1. Location in patent: Paragraph 0755
[4] Journal of Medicinal Chemistry, 1997, vol. 40, # 5, p. 811 - 818
[5] Russian Journal of Organic Chemistry, 2001, vol. 37, # 4, p. 564 - 569
