1. A suspension of 1-fluoro-3-iodo-5-nitrobenzene (0.5 g, 1.87 mmol) with SnCl2-2H2O (1.5 g, 6.64 mmol) in ethanol (10 mL) was heated to reflux for 1.5 hours. After completion of the reaction, the solvent was removed under reduced pressure and the crude product was diluted with ether and washed sequentially with 4N NaOH solution and saturated saline. The ether layer was separated, dried with anhydrous Na2SO4, filtered and concentrated to give the amine compound as a solid (0.4 g, 91% yield). The crude product can be used directly in the next step of the reaction.
2. A mixture of amine (0.4 g, 1.69 mmol), iodomethane (0.719 g, 5 mmol) and potassium carbonate (0.46 g, 3.38 mmol) obtained above in N,N-dimethylformamide (DMF; 10 mL) was stirred at room temperature for 48 hours. After completion of the reaction, water (10 mL) was added and extracted three times with ether. The organic extracts were combined, washed sequentially with water and saturated saline, dried over anhydrous Na2SO4, filtered and concentrated. The crude product was purified by column chromatography to afford 3-fluoro-5-iodo-N,N-dimethylaniline (VMY-2-119) as liquid (0.23 g, 52% yield).
1H NMR (399 MHz, CDCl3) δ: 6.69-6.63 (m, 2H), 6.22 (dt, J = 12.5, 2.3 Hz, 1H), 2.83 (s, 6H).
13C NMR (100 MHz, CDCl3) δ: 163.33 (d, JF-C = 245 Hz), 152.49 (d, J = 11 Hz), 116.91 (d, J = 2.4 Hz), 112.12 (d, J = 24 Hz), 98.73 (d, J = 26 Hz), 94.24 (d, J = 11 Hz), 40.21 (s, 3H). 40.21 (s, 3H).
