Uses
2-Nitroisophthalic Acid is an intermediate in the synthesis of 2,6-Dihydroxymethyl Rilpivirine (D446615), which is an analog of Rilpivirine (R509800) a novel non-nucleoside reverse transcriptase inhibitor. Rilpivirine seems to be well tolerated with less CNS disturbance than Efavirenz, and has non-teratogenic potential. An anti-HIV agent.
Synthesis
General procedure for the synthesis of 2-nitro-isophthalic acid from 2,6-dimethylnitrobenzene: Potassium permanganate (643 g, 4.07 mol, 4.0 eq.) was added to a solution of sodium hydroxide (135 g, 3.38 mol, 3.3 eq.) in water (4080 mL) at room temperature. 2-Nitro-m-xylene (153 g, 1.01 mol, 1.0 eq.) was then added and the resulting mixture was stirred vigorously under strong reflux conditions. The purple color of the reaction mixture gradually faded with the reduction of potassium permanganate and the reaction continued for 12 hours. After completion of the reaction, the suspension was cooled to room temperature and filtered through a sintered funnel. The yellow filtrate obtained was carefully acidified with concentrated sulfuric acid (98%, 200 mL) to a pH below 2. The white solid formed was collected by filtration and washed with dichloromethane to recover unreacted feedstock (31.9 g). The crude product white filter cake was washed with ethyl acetate and filtered. The insoluble white solid was discarded and the filtrate was dried with anhydrous magnesium sulfate. Finally, the solvent was evaporated under vacuum to give pure 2-nitroisophthalic acid (112 g, 52% yield), and the crude product was used directly in the next reaction. (CAS No.: 21161-11-5)
References
[1] Synthesis (Germany), 2015, vol. 47, # 24, p. 3859 - 3873
[2] Angewandte Chemie - International Edition, 2004, vol. 43, # 20, p. 2661 - 2665
[3] Chemistry Letters, 2015, vol. 44, # 5, p. 677 - 679
[4] Journal of the American Chemical Society, 2012, vol. 134, # 31, p. 13103 - 13107
[5] Patent: WO2014/85528, 2014, A1. Location in patent: Page/Page column 43; 49; 50
