Synthesis
The general procedure for the synthesis of 2-fluoro-5-iodonitrobenzene from 1-fluoro-2-nitrobenzene is as follows:
Intermediate Example 3. Synthesis of 1-fluoro-4-iodo-2-nitrobenzene
To a solution of trifluoromethanesulfonic acid (15.6 ml, 177.15 mmol, 5 eq.) of 1-fluoro-2-nitrobenzene (5 g, 35.43 mmol) was added N-iodosuccinimide (9.57 g, 42.5 mmol, 1.2 eq.) in one batch at 0 °C. The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, the reaction was quenched by addition of water and extracted with diethyl ether (3 x 150 ml). The organic layers were combined and washed sequentially with water, aqueous sodium thiosulfate and brine and then dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure and the crude product obtained was purified by column chromatography (60-120 mesh silica gel, 5% ethyl acetate in hexane solution as eluent) to afford the target compound 1-fluoro-4-iodo-2-nitrobenzene in 66% yield (6.2 g).
1H NMR (300 MHz, DMSO-d6): δ 8.42 (dd, 1H), 8.18-8.13 (m, 1H), 7.46-7.39 (m, 1H).
References
[1] Journal of the American Chemical Society, 2004, vol. 126, # 48, p. 15770 - 15776
[2] Patent: WO2013/53983, 2013, A1. Location in patent: Page/Page column 30
[3] Patent: US2015/11548, 2015, A1. Location in patent: Paragraph 0132
[4] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1973, p. 595 - 599
