Synthesis
General procedure for the synthesis of 6-methoxybenzothiazole from 2-amino-6-methoxybenzothiazole: To a solution of tetrahydrofuran (THF, 100 mL) containing Example 18a (11.7 g, 0.065 mol) was added isoamyl nitrite (15.2 g, 0.13 mol) under nitrogen protection. The reaction mixture was stirred at 70 °C for 2 hours. Upon completion of the reaction, the reaction was quenched by the addition of water (500 mL), followed by extraction with ethyl acetate (EA, 500 mL x 2). The organic layers were combined, washed with brine (200 mL) and dried over anhydrous sodium sulfate (Na2SO4). After filtration, the filtrate was concentrated and purified by fast column chromatography to afford the target product 6-methoxybenzothiazole (Example 18b, 10.2 g, 95% yield) as a colorless oil.LCMS analysis showed [M + 1]+ = 166.
References
[1] Patent: WO2017/218960, 2017, A1. Location in patent: Paragraph 00453
[2] Chemical and Pharmaceutical Bulletin, 1997, vol. 45, # 9, p. 1547 - 1549
[3] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 20, p. 5435 - 5438
[4] Tetrahedron, 1997, vol. 53, # 50, p. 17029 - 17038
[5] Organic and Biomolecular Chemistry, 2017, vol. 15, # 10, p. 2246 - 2252
