Synthesis
General procedure for the synthesis of 1-(2-bromoethyl)-3-chlorobenzene from 3-chlorobenzene ethanol: Triphenylphosphine (3.90 g, 14.9 mmol) was added to a stirred solution containing 3-chlorobenzene ethanol (2.0 mL, 14.8 mmol), carbon tetrabromide (4.91 g, 14.8 mmol), and anhydrous dichloromethane (100 mL), under nitrogen protection. The reaction mixture was stirred at room temperature for 5 hours. After completion of the reaction, the reaction mixture was washed sequentially with water (100 mL) and brine (100 mL). The organic layer was separated, dried with magnesium sulfate, filtered and concentrated on a rotary evaporator to give the crude product. The crude product was purified by rapid chromatography on silica gel using 100% hexane as eluent to give 2.30 g (71% yield) of 1-(2-bromoethyl)-3-chlorobenzene. Thin layer chromatography (TLC) analysis: Rf value was 0.27 in 100% hexane; 1H NMR (CDCl3) data: δ 7.26-7.11 (m, 3H), 7.09-7.07 (m, 1H), 3.54 (t, 2H), 3.12 (t, 2H).
References
[1] Journal of Medicinal Chemistry, 1996, vol. 39, # 20, p. 4017 - 4026
[2] Patent: WO2004/26305, 2004, A1. Location in patent: Page/Page column 67-68
[3] Patent: US2002/19531, 2002, A1
[4] Journal of the Chemical Society, 1964, p. 1548 - 1553
[5] Tetrahedron Asymmetry, 1998, vol. 9, # 15, p. 2725 - 2737
