Chemical Properties
Clear colorless to pale yellow liquid
Uses
2-Bromo-4-chloroanisole has been used as a reactant in the preparation of naphthyl phenyl ethers as nonnucleoside HIV-1 reverse transcriptase inhibitors.
Synthesis
General procedure for the synthesis of 2-bromo-4-chloroanisole from 2-bromo-4-chlorophenol and iodomethane: In a 250 mL round-bottomed flask, 2-bromo-4-chlorophenol (16.94 g, 81.6 mmol, 1.0 eq.) was dissolved in acetone (160 mL), and iodomethane (6.10 mL, 98 mmol, 1.2 eq.), potassium carbonate (12 g), and water (4 mL). The reaction mixture was heated to reflux for 3 h. After cooling to room temperature, most of the volatiles were removed under reduced pressure. The residue was poured into water (140 mL) and extracted with ethyl acetate (3 x 150 mL). The organic phases were combined, washed with brine (1 x 100 mL), dried (K2CO3), filtered through a pad of diatomaceous earth and concentrated to give a clear oil. Purification by short-range distillation (80°-85 °C, 1 Torr) afforded 17.74 g (98% yield) of 2-bromo-4-chloroanisole as a clear liquid. 2-bromo-4-chloroanisole was characterized by NMR hydrogen spectroscopy (400 MHz, acetone-d6) with the following data: δ 7.53 (d, J = 2.5 Hz, 1H); 7.24 (dd, J = 9.7, 2.5 Hz. 1H); 6.81 (d, J = 9.7 Hz, 1H); 3.88 (s, 3H).
References
[1] Angewandte Chemie - International Edition, 2008, vol. 47, # 27, p. 5067 - 5070
[2] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 14, p. 4220 - 4226
[3] Angewandte Chemie - International Edition, 2014, vol. 53, # 25, p. 6443 - 6448
[4] Angew. Chem., 2014, vol. 126, # 25, p. 6561 - 6566
[5] Patent: US5688808, 1997, A
