Uses
4-Bromo-2,6-difluoroaniline is used in the preparation of potent, VEGF receptor tyrosine kinase inhibitors.
Synthesis
b) Preparation of Intermediate 2: Dissolve 2,6-difluoroaniline (3.0 g, 22.56 mmol) in acetic acid (10 mL). Bromine (1.2 mL) was slowly added dropwise to the above solution. The reaction mixture was stirred at room temperature for 15 minutes. After the reaction was completed, the solvent was evaporated under reduced pressure. The residue was neutralized with aqueous sodium carbonate and the aqueous phase was subsequently extracted with dichloromethane. The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give Intermediate 2 in 92% yield.
References
[1] Angewandte Chemie - International Edition, 2016, vol. 55, # 4, p. 1544 - 1547
[2] Angew. Chem., 2016, vol. 128, # 4, p. 1569 - 1573,5
[3] Journal of Materials Chemistry C, 2016, vol. 4, # 23, p. 5326 - 5333
[4] Patent: WO2006/15985, 2006, A1. Location in patent: Page/Page column 54
[5] Patent: US6716491, 2004, B2
