Synthesis
General procedure for the synthesis of 6-bromo-2-methyl-1,3-benzothiazole from N-(4-bromo-2-iodophenyl)acetamide: N-(4-bromo-2-iodophenyl)acetamide (678 mg, 2.00 mmol) was dissolved in N,N-dimethylformamide (4.00 mL), followed by the addition of sodium sulfide nonahydrate (721 mg, 6.00 mmol) and copper iodide (I) (38.0 mg, 0.200 mmol). The reaction mixture was stirred at 80 °C. After the reaction was completed, it was cooled to room temperature, concentrated hydrochloric acid (1.6 mL) was added, and stirring was continued at 80 °C for 12 hours. At the end of the reaction, saturated aqueous sodium bicarbonate solution (20 mL) was added to neutralize. Extraction was performed with ethyl acetate (50 mL x 2). The organic layers were combined, washed with saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure and the residue was purified by silica gel column chromatography to afford 6-bromo-2-methyl-1,3-benzothiazole (134 mg, 29.5% yield) using hexane/ethyl acetate (4:1, v/v) as eluent.
References
[1] Angewandte Chemie, International Edition, 2009, vol. 48, # 23, p. 4222 - 4225
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 18, p. 7241 - 7257
[3] Patent: JP2016/79108, 2016, A. Location in patent: Paragraph 0055
[4] Patent: JP2015/89879, 2015, A. Location in patent: Paragraph 0016; 0037; 0038; 0040
