Synthesis
Example 17A-1 Synthesis of 2-chloro-5-nitrobenzenesulfonamide: 2-chloro-5-nitrobenzenesulfonic acid (104 g, 437.6 mmol) was dissolved in thionyl chloride (240 mL), followed by the addition of N,N-dimethylformamide (2 mL) as a catalyst. The reaction mixture was heated to reflux and maintained for 4 hours to complete the reaction. Upon completion of the reaction, the mixture was carefully poured into water for quenching and the product was subsequently isolated by filtration. The resulting 2-chloro-5-nitrobenzenesulfonyl chloride was dissolved in toluene and slowly added to a pre-mixed solution of NH4OH (520 mL) and tetrahydrofuran (520 mL) at -10 °C. The reaction mixture was stirred at this temperature for 1 h. The reaction was quenched with 6 M hydrochloric acid solution and the final pH was adjusted to 4. After separating the aqueous and organic layers, the organic layer was concentrated to dryness to give a powdery product. To this powdered product pentane was added and the target compound was isolated by filtration and dried to give 2-chloro-5-nitrobenzenesulfonamide (82.6 g, 80% yield).
References
[1] European Journal of Medicinal Chemistry, 2012, vol. 50, p. 18 - 26
[2] Patent: US2011/152246, 2011, A1. Location in patent: Page/Page column 293
[3] Patent: US2005/107364, 2005, A1. Location in patent: Page/Page column 75
[4] Patent: WO2005/19191, 2005, A2. Location in patent: Page/Page column 151
[5] Journal of Pharmacy and Pharmacology, 2001, vol. 53, # 5, p. 669 - 680
