Uses
2,6-Difluoro-3,5-dimethoxyaniline is an organic compound used primarily as an organic synthesis intermediate and a pharmaceutical intermediate, especially in laboratory research and development and chemical production processes. The compound is a key intermediate in the drug pemigatinib, used to treat certain types of cancer.
Synthesis
Tert-butyl 2,6-difluoro-3,5-dimethoxyphenylcarbamate (34.6 g, 0.12 mol) was added to 120 mL of trifluoroacetic acid and stirred until completely dissolved to form a homogeneous solution. The reaction mixture was stirred at room temperature for 30 minutes. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. To the residue, saturated sodium bicarbonate solution was slowly added to adjust the pH to 8. The resulting suspension was extracted twice with diethyl ether (appropriate amount each time). The organic phases were combined, washed once with saturated saline, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 22 g of 2,6-difluoro-3,5-dimethoxyaniline in 97% yield. The mass spectrum (APCI) showed (M+1)/z of 190.1.
References
[1] Patent: WO2006/38112, 2006, A1. Location in patent: Page/Page column 28
[2] Patent: US2004/19210, 2004, A1. Location in patent: Page 13
