Synthetic Route of 33070-32-5, A common heterocyclic compound, 33070-32-5, name is 5-Bromo-2,2-difluorobenzodioxole, molecular formula is C7H3BrF2O2, its 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.
To a cold solution of 5-bromo-2,2-difluorobenzo[(f] [l ,3]dioxole (5.75 mL, 42.2 mmol) in tetrahydrofuran (80 mL) was added a 2.0 M solution of isopropylmagnesium chloride in tetrahydrofuran (28.1 mL, 56.1 mmol) within 5- 10 minutes while maintaining the temperature in the range of 10-20 C. The reaction mixture was stirred at the same temperature for another 15 minutes and then allowed to attain room temperature with continued overnight stirring. The reaction mixture was cooled with an ice bath, triisopropyl borate (12.74 mL, 54.9 mmol) was added dropwise over 2 minutes, and stirring at room temperature was continued for 30 minutes. The reaction mixture was cooled to 10 C and 10% H2SO4 solution (50 mL) was added slowly which resulted in a slight exotherm to 20 C. After stirring for 15 minutes, the mixture was partitioned between water and ethyl acetate, and the combined organic extracts were washed with saturated NaHCC>3 solution. The organic layer was separated, dried over magnesium sulfate, filtered, and concentrated. The residue was dissolved in 100 mL of teri-butyl methyl ether and cooled to 0 C. 30% Hydrogen peroxide solution in water (5.39 mL, 52.7 mmol) was added slowly, followed by water (60 mL), and the mixture was stirred overnight while warming up to ambient temperature. The reaction mixture was diluted with ethyl acetate and washed twice with sodium thiosulfate solution and brine. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated, and the residue was purified on silica gel(0-50% ethyl acetate in heptane) to give 6.43 g of the title compound as an amber oil.JH NMR (400 MHz, DMSO- ) delta ppm 9.75 (s, 1H), 7.12 (d, / = 8.7 Hz, 1H), 6.75 (d, / = 2.4 Hz, 1H), 6.52 (dd, / = 8.7, 2.5 Hz, 1H). MS (ESI-) mJz 173.1 (M-H)
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; CALICO LIFE SCIENCES LLC; ABBVIE INC.; MARTIN, Kathleen, Ann; SIDRAUSKI, Carmela; PLIUSHCHEV, Marina, A.; FROST, Jennifer, M.; TONG, Yunsong; BLACK, Lawrence, A.; XU, Xiangdong; SHI, Lei; ZHANG, Qingwei, I.; CHUNG, Seungwon; XIONG, Zhaoming; SWEIS, Ramzi, Farah; DART, Michael, J.; BROWN, Brian, S.; MURAUSKI, Kathleen; (673 pag.)WO2019/90069; (2019); A1;,
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