Synthesis
General procedure for the synthesis of 4-bromo-2-chloro-1-isopropoxybenzene from 4-bromo-2-chlorophenol and 2-bromopropane: K2CO3 (100 g) and 2-bromopropane (136 mL) were added in one go to a stirred N,N-dimethylformamide (DMF) (250 mL) solution of 4-bromo-2-chlorophenol (50 g) at room temperature, under nitrogen protection. The reaction mixture was stirred at 85°C for 16 hours. After completion of the reaction, it was cooled to room temperature, the reaction mixture was filtered and the solvent in the filtrate was removed by distillation under reduced pressure. The residue was dissolved in ether (300 mL) and the organic phase was washed with water (6 x 100 mL) and subsequently dried and concentrated with MgSO4 to give 4-bromo-2-chlorophenyl 1-methylethyl ether (D10) (56 g) as a yellow oil. δH (CDCl3, 400 MHz): 1.37 (6H, d), 4.52 (1H, m), 6.82 (1H , d), 7.29 (1H, m), 7.50 (1H, d).
References
[1] Patent: WO2010/148649, 2010, A1. Location in patent: Page/Page column 85
[2] Patent: WO2011/113309, 2011, A1. Location in patent: Page/Page column 24-25
[3] Patent: US2011/269738, 2011, A1. Location in patent: Page/Page column 33
[4] Patent: WO2011/134280, 2011, A1. Location in patent: Page/Page column 66; 67
[5] Patent: US2013/12491, 2013, A1. Location in patent: Paragraph 0159; 0160
