Synthetic Route of 82830-49-7,Some common heterocyclic compound, 82830-49-7, name is 2-Fluoro-1,4-dimethoxybenzene, molecular formula is C8H9FO2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
A 10 mL oven-dried Schlenk tube was charged with magnesium (57.6 mg, 2.4 mmol) and anhydrous THF (1.5 mL), 5 drops of diisobutylaluminium hydride (DIBAL) was added and stirred for 5 min to activate magnesium. 3-bromo-2,4,6-triisopropyl-4?-(trifluoromethyl)-1,1?-biphenyl (852 mg, 2 mmol) was added potion-by-potion with vigorous stirring. The tube was capped with a rubber septum and was heated to 70 C. for 2 h (A). In another 10 mL oven-dried Schlenk tube was charged with 2-fluoro-1,4-dimethoxybenzene (156 mg, 1 mmol) and anhydrous THF (3.5 mL). The tube was cooled to -78 C. and 1.6 M n-BuLi solution in hexane (0.64 mL, 1 mmol) was added dropwise over 10 min under vigorous stirring. The mixture was stirred at -78 C. for 40 min (B). A was transferred into to B by syringe over 15 min at -78 C. An additional 1 mL of THF was used to rinse the reaction and was also transferred to B. The combined reaction mixture was stirred at -78 C. for another 1 h and then slowly warmed to room temperature and vigorously stirred for overnight. At this time, the mixture was cooled to 0 C. using ice bath, and iodine (762 mg, 3 mmol) in 4 mL anhydrous THF was added drop-wise over 5 min, then the reaction mixture was stirred for 30 min, and then warmed to stir at room temperature for 2 h. Then, the mixture was quenched with saturated Na2S2O3 (aq.) solution until the red color of bromine disappeared. The aqueous phase was extracted with Et2O (10 mL¡Á3) and the combined organic phases were dried over anhydrous MgSO4. After concentration, the crude product was purified by silica gel chromatography (EtOAc/petroleum ether=1/20) followed by crystallization in methanol to get a white solid (226 mg, 37%), labeled as 25MeOTIP-I. 1H NMR (600 MHz, Chloroform-d) delta 7.66-7.61 (m, 3H), 7.46-7.39 (m, 2H), 7.23 (s, 1H), 6.90 (d, J=8.9 Hz, 1H), 6.82 (d, J=8.9 Hz, 1H), 3.91 (s, 3H), 3.71 (s, 3H), 2.65 (p, J=7.2 Hz, 1H), 2.37 (dp, J=25.3, 6.9 Hz, 2H), 1.23 (d, J=6.8 Hz, 3H), 1.11 (dd, J=10.3, 6.9 Hz, 6H), 1.04 (d, J=6.9 Hz, 3H), 0.80 (d, J=7.2 Hz, 3H), 0.71 (d, J=7.2 Hz, 3H) ppm. 13C NMR (151 MHz, Chloroform-d) delta 152.40 (d, J=40.7 Hz), 147.01, 146.10, 145.85, 141.68, 137.11 (d, J=48.9 Hz), 136.32, 132.12, 131.30, 128.68 (d, J=32.3 Hz), 124.02, 119.94, 110.00, 109.30, 56.81, 55.31, 32.51, 30.93, 29.72, 24.61 (d, J=4.2 Hz), 24.00, 23.69, 22.94 (d, J=12.1 Hz) ppm. 19F NMR (376 MHz, CDCl3) delta=-62.15 ppm.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Fluoro-1,4-dimethoxybenzene, its application will become more common.
Reference:
Patent; Agency for Science, Technology and Research; Johannes, Charles W.; Robins, Edward G.; Jong, Howard; Lim, Yee Hwee; Chia, Saei Weng; Yang, Yong; Podichetty, Anil; (84 pag.)US2016/207034; (2016); A1;,
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