Uses
6-Bromo-3 H-isobenzofuran-1-one serves as a starting material for the synthesis of 3-chloro-5-({2-oxo-1-[(3-oxo-1,3-dihydroisobenzofuran-5-yl)methyl]-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl}oxy)benzonitrile[6].
Synthesis
Step c: Synthesis of 6-bromoisobenzofuran-1(3H)-one
Aqueous (22 mL) solution of NaNO2 (2.2 g, 0.040 mol) was added dropwise to a suspension of 6-aminoisobenzofuran-1(3H)-one (5.0 g, 0.030 mol) in HBr (70 mL, 48%), keeping the reaction temperature at 0 °C. After completion of dropwise addition, stirring of the reaction mixture was continued for 20 min. Subsequently, the reaction solution was transferred to a pre-cooled solution of CuBr (22 g, 0.21 mol) in HBr (48%, 23 mL). The resulting dark brown mixture was stirred for 20 min and then diluted with deionized water (200 mL) to precipitate an orange precipitate. The precipitate was collected by filtration, washed with saturated NaHCO3 solution and subsequently extracted with ethyl acetate (20 mL x 3). The organic phases were combined, dried with anhydrous Na2SO4 and concentrated under reduced pressure to afford 6-bromoisobenzofuran-1(3H)-one (5.4 g, 84% yield).
1H NMR (300 MHz, CDCl3) δ 8.05 (d, J = 1.8 Hz, 1H), 7.80 (dd, J = 8.1, 1.8 Hz, 1H), 7.39 (d, J = 8.1 Hz, 1H), 5.28 (s, 2H).
References
[1] Patent: US2008/9524, 2008, A1. Location in patent: Page/Page column 410
[2] Patent: EP1362856, 2003, A1. Location in patent: Page/Page column 159
[3] Patent: US2015/231142, 2015, A1. Location in patent: Paragraph 1265
[4] Chemistry of Heterocyclic Compounds, 2010, vol. 46, # 2, p. 140 - 145
[5] Journal of Medicinal Chemistry, 2015, vol. 58, # 9, p. 3997 - 4015
[6] ElMarrouni, A., Suen, L., Wang, C., Hunter, D., Mitchell, H., & Converso, A. (2018). Synthesis of HIV NNRTI Doravirine Analogues via Visible-Light Photoredox Decarboxylative Cross-Coupling. Synthesis, 50(16), 3177–3186.
https://doi.org/10.1055/s-0037-1610155
