Synthesis
General procedure for the synthesis of 3-bromo-4-methoxybenzene-1-sulfonyl chloride from 2-bromoanisole: 2-bromo-1-methoxybenzene (1.87 g, 10.0 mmol) was dissolved in chloroform (5 mL), and the solution was cooled in an iced salt bath to -5 °C to 0 °C. Chlorosulfonic acid (2.0 mL, 30.0 mmol) was slowly added dropwise over 30 minutes, and after completion of the dropwise addition, the reaction mixture was gradually warmed to room temperature over 1 hour. Subsequently, the reaction mixture was poured onto crushed ice and transferred to a dispensing funnel. The aqueous layer was separated and extracted twice with chloroform. The organic layers were combined, dried and concentrated to give 3-bromo-4-methoxybenzenesulfonyl chloride (2.80 g, 98%). 3-Bromo-4-methoxybenzenesulfonyl chloride (2.80 g, 9.8 mmol) was dissolved in dichloromethane (30 mL), triethylamine (1.76 mL, 12.6 mmol) was added to the solution, followed by slow dropwise addition of tert-butylamine (1.33 mL, 12.6 mmol). The reaction mixture was allowed to stand for 2 hours and then poured into a mixture of 5% citric acid solution and dichloromethane. The organic layer was separated and the aqueous layer was extracted twice with dichloromethane. The organic layers were combined, dried and concentrated. The crude product was recrystallized by ethyl acetate/hexane mixed solvent to give 3-bromo-N-tert-butyl-4-methoxybenzenesulfonamide (2.43 g, 77%).
References
[1] Patent: WO2004/50637, 2004, A2. Location in patent: Page 68-69
[2] Patent: WO2004/62661, 2004, A1. Location in patent: Page/Page column 24-25; 37-38
[3] Patent: US2015/25068, 2015, A1. Location in patent: Paragraph 0794
[4] Journal of the Chemical Society [Section] C: Organic, 1969, p. 1341 - 1345
[5] Bioorganic and Medicinal Chemistry Letters, 1997, vol. 7, # 4, p. 485 - 488
