Synthesis
To a 500-mL round-bottomed flask was added 15.6 g of polyphosphoric acid (PPA) and anhydrous chlorobenzene (260 mL). The mixture was heated to reflux and a solution of 1-bromo-2-(2,2-dimethoxyethoxy)-4-methylbenzene (8.11 g, 29.5 mmol) dissolved in chlorobenzene (60 mL) was added slowly and dropwise over 2 hours. The reflux reaction was maintained for 3 hours and then cooled to room temperature. The reaction mixture was filtered through a silica plug and subsequently concentrated. Purification by column chromatography (eluent: 100% hexane) afforded 4.67 g (75% yield) of the target product 7-bromo-4-methyl-benzofuran as a white, waxy solid with a melting point of 32-33 °C. 1H NMR (300 MHz, DMSO-d6) δ: 2.46 (3H, single peak), 7.02 (1H, double peak, J=7.9 Hz), 7.16 ( 1H, double peak, J=2.2 Hz), 7.43 (1H, double peak, J=7.9 Hz), 8.10 (1H, double peak, J=2.2 Hz). Mass spectrum (EI) m/z: 210 ([M+]). Elemental analysis (C9H7BrO) Calculated value: C: 51.22, H: 3.34; measured value: C: 50.83, H: 3.08.
References
[1] Patent: WO2004/103941, 2004, A2. Location in patent: Page 27
[2] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 4, p. 902 - 906
