Uses
5-Bromo-2,2-dimethylbenzo[d][1,3]dioxole is used as a reactant in the preparation of phenanthridine-based Bcl-XL inhibitors.
Synthesis
General procedure for the synthesis of 5-bromo-2,2-dimethylbenzo[d][1,3]dioxolane from 2,2-dimethylbenzo[d][1,3]dioxolane: 2,2-dimethyl-2H-1,3-benzo[d]dioxolane (1.00 g, 6.66 mmol) was dissolved in anhydrous N,N-dimethylformamide (20 mL). N-bromosuccinimide (1.19 g, 6.66 mmol) was added batchwise at room temperature. The reaction mixture was stirred at the same temperature overnight. Analysis by liquid chromatography-mass spectrometry (LCMS) showed almost complete consumption of the starting material. The reaction process was difficult to monitor by TLC as the starting material and the product had the same Rf value on thin layer chromatography (TLC). Upon completion of the reaction, the mixture was diluted with water, appropriate amount of saturated saline was added, followed by ethyl acetate for extraction. The organic and aqueous phases were separated and the organic phase was dried with anhydrous magnesium sulfate, filtered and concentrated to dryness. The crude product was purified by silica gel column chromatography with the eluent cyclohexane/ethyl acetate (95:5, v/v). The product-containing fraction was collected and concentrated to dryness to afford 5-bromo-2,2-dimethyl-2H-1,3-benzodioxole (1.32 g, 86% yield) as a colorless oil.1H NMR (300 MHz, DMSO-d6, δ/ppm): 1.63 (s, 6H), 6.79 (d, 1H, J = 8.1Hz), 6.95 (dd , 1H, J = 8.1Hz, J = 2.1Hz), 7.06 (d, 1H, J = 2.1Hz).
References
[1] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 22, p. 4133 - 4137
[2] Patent: WO2018/138362, 2018, A1. Location in patent: Page/Page column 68; 130; 131
[3] Heterocycles, 2014, vol. 88, # 2, p. 1121 - 1133
[4] ChemMedChem, 2018, vol. 13, # 21, p. 2332 - 2348
[5] Molecules, 2015, vol. 20, # 5, p. 8654 - 8665
