Synthesis
The general procedure for the synthesis of 2-iodo-4,5-difluoroaniline using 3,4-difluoroaniline as starting material was as follows: 3,4-difluoroaniline (645 mg, 5 mmol) was suspended in distilled water (25 mL). Sodium bicarbonate (630 mg, 7.5 mmol) was then added, followed by iodine monomer (1.65 g, 6.5 mmol). The reaction mixture was stirred vigorously at room temperature (~25°C) for 30 minutes. Upon completion of the reaction, the mixture was poured into saturated sodium thiosulfate solution (50 mL) to quench the reaction. Extraction was carried out with ethyl acetate (2 x 25 mL) and the organic phases were combined. The organic phase was washed sequentially with sodium thiosulfate solution (20 mL), distilled water (20 mL) and saturated saline (20 mL) to remove unreacted iodine and other water-soluble impurities. The washed organic phase was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to afford 2-iodo-4,5-difluoroaniline as a dark colored oil (1.24 g, 97% yield).
References
[1] Patent: WO2006/82400, 2006, A1. Location in patent: Page/Page column 55
[2] Tetrahedron Letters, 2005, vol. 46, # 6, p. 907 - 910
[3] Organic Letters, 2008, vol. 10, # 13, p. 2657 - 2659
[4] Patent: EP2141164, 2010, A1. Location in patent: Page/Page column 44
[5] Journal of Fluorine Chemistry, 2012, vol. 135, p. 97 - 107
