Synthesis
The general procedure for the synthesis of 2-bromo-3'-nitroacetophenone from m-nitroacetophenone is as follows: preparation of 2-bromo-1-(3-nitrophenyl)acetophenone (2a-1). Aluminum chloride (0.16 g, 1.20 mmol) was added to a suspension of commercially available 3-nitroacetophenone (4.82 g, 29.19 mmol) in anhydrous ether (25 mL). The reaction mixture was cooled to 0 °C, followed by the slow dropwise addition of bromine (1.50 mL, 29.19 mmol). The reaction mixture was stirred at room temperature for 1 h until complete conversion of the feedstock (monitored by 1H NMR) and the reaction was quenched quickly to avoid dibromide formation. After addition of water (30 mL), the mixture was extracted with ether (3 x 30 mL) and dried over anhydrous magnesium sulfate to afford compound 2a-1 as a yellow-brown solid (5.73 g, 97% yield).1H NMR (CDCl3, 200 MHz): δ 4.50 (s, 2H, H1), 7.73 (t, J = 8.0 Hz, 1H, H7), 8.31 ( ddd, J = 7.8, 1.7, 1.1 Hz, 1H, H8), 8.43 (ddd, J = 8.2, 2.3, 1.1 Hz, 1H, H6), 8.76 (t, J = 1.9 Hz, 1H, H4).13C NMR (CDCl3, 200 MHz): δ 30.4, 123.9, 128.2, 130.4, 134.6, 135.2, 148.6, 189.5. MS-ESI (m/z): [M + H]+ = 244.9.
References
[1] Journal of Medicinal Chemistry, 2016, vol. 59, # 18, p. 8276 - 8292
[2] Patent: WO2017/17004, 2017, A1. Location in patent: Page/Page column 17
[3] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 10, p. 2192 - 2196
[4] Tetrahedron Letters, 2011, vol. 52, # 31, p. 4026 - 4029
[5] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2009, vol. 48, # 10, p. 1424 - 1430
