Synthesis
Step A: Sodium nitrite (0.9 g, 13 mmol) was added in batches to a suspension of 2-methyl-5-aminobenzothiazole dihydrochloride (2.0 g, 8 mmol) in hydrobromic acid (24 ml) at 0 °C. The resulting mixture was slowly added dropwise to a solution of copper (I) bromide (4.0 g, 14 mmol) in hydrobromic acid (50 ml) at 0°C. The reaction mixture was stirred continuously at 0 °C for 2 h before the reaction was terminated by the addition of water. The pH of the reaction mixture was adjusted to 9 with aqueous ammonium hydroxide and subsequently extracted with ethyl acetate. The organic layers were combined, dried with magnesium sulfate and purified by column chromatography (eluent ratio 9:1 heptane/ethyl acetate) to afford the target product 2-methyl-5-bromobenzothiazole (1.0 g, 52% yield, 82% GC purity). The structure of the product was confirmed by 1H NMR (300 MHz, DMSO-d6): δ 8.12 (d, J=1.8 Hz, 1H), 8.02 (dd, J=8.4,1.5 Hz, 1H), 7.56 (dd, J=8.7,2.1 Hz, 1H), 2.81 (s, 3H).
