Synthesis
General procedure for the synthesis of 2-bromo-2'-fluoroacetophenone from o-fluoroacetophenone: bromine (5.8 mL) was added slowly and dropwise to a solution of 1-(2-fluorophenyl)ethanone (15.1 g) in acetic acid (150 mL). The reaction mixture was stirred at room temperature for 2 h. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. The residue was dissolved in saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic phase was washed sequentially with saturated aqueous sodium bicarbonate, water and saturated brine and dried over anhydrous magnesium sulfate. After filtration, the organic phase was concentrated under reduced pressure to afford 2-bromo-2'-fluoroacetophenone (22.91 g, 97% yield) as a light yellow oil. The product was characterized by 1H-NMR (CDCl3): δ 4.53 (2H, d, J = 2.4 Hz), 7.13-7.20 (1H, m), 7.27-7.30 (1H, m), 7.54-7.61 (1H, m), 7.91-7.96 (1H, m).
References
[1] Patent: US2009/156642, 2009, A1. Location in patent: Page/Page column 40
[2] Patent: EP2196459, 2010, A1. Location in patent: Page/Page column 78
[3] Tetrahedron Letters, 2012, vol. 53, # 2, p. 191 - 195
[4] Journal of Medicinal Chemistry, 1998, vol. 41, # 20, p. 3763 - 3772
[5] Journal of Medicinal Chemistry, 2014, vol. 57, # 15, p. 6572 - 6582
