Preparation
Obtained by reaction of acetic anhydride with o-bromoanisole in the presence of lithium perchlorate at 100° for 5 h (99%).
Synthesis
General procedure for the synthesis of 1-(3-bromo-4-methoxyphenyl)ethanone from p-methoxyacetophenone: ketone 7a (5.0 g, 33.3 mmol) and N-bromosuccinimide (NBS, 5.9 g, 33.3 mmol) were dissolved in 100 mL of water and heated to 60 °C. Subsequently, 40% H2SO4 (66.7 mmol, 8.9 mL) was added slowly and dropwise. The reaction mixture was stirred continuously for 5 hours. After completion of the reaction, the mixture was cooled to room temperature and separated by extraction with ethyl acetate (60 mL x 3). The organic phases were combined, washed with saturated NaHCO3 solution, dried over anhydrous MgSO4 and concentrated under reduced pressure to give the crude product 7b (7.5 g, 98% yield) as a white solid. Thin layer chromatography (TLC) Rf value was 0.85 (petroleum ether/ethyl acetate, 3:1).1H NMR (400 MHz, DMSO-d6) δ: 3.09 (3H, s), 3.93 (3H, s), 3.95 (6H, s), 7.92 (1H, d, J = 8.9 Hz), 7.97 (1H, dd, J = 2.1 Hz, 8.9 Hz), 8.10 (2H, d, J = 2.1 Hz); LC-MS m/z: 230.9 [M + H]+.
References
[1] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 17, p. 4372 - 4376
[2] Tetrahedron, 2017, vol. 73, # 50, p. 7105 - 7114
[3] Synthetic Communications, 2014, vol. 44, # 2, p. 181 - 187
[4] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 13, p. 3618 - 3628
[5] Organic Letters, 2013, vol. 15, # 9, p. 2108 - 2111
