1101120-80-2

859855-53-1

1101120-80-2

General procedure for the synthesis of 2-fluoro-5-cyanobenzenesulfonyl chloride from 3-amino-4-fluorobenzonitrile: An aqueous solution (2 mL) of NaNO2 (380 mg, 5.51 mmol) was slowly added to a suspension of 3-amino-4-fluorobenzonitrile (500 mg, 3.67 mmol) in concentrated HCl (5 mL) at 0 °C. The reaction mixture was kept stirred at 0 °C for 30 min. Meanwhile, SO2-saturated AcOH solution (5 mL) was prepared, followed by the addition of CuCl2-2H2O (188 mg, 1.10 mmol) and continued to pass SO2 gas for 5 min. This AcOH mixture was cooled to 5 °C and then the diazonium salt solution prepared as previously described was added over 5 min. The reaction mixture was continued to be stirred at 0°C for 1 hour, followed by warming up to room temperature and stirring for another 1 hour. After completion of the reaction, the mixture was diluted with water and extracted twice with CH2Cl2. The organic phases were combined, washed twice with water, dried over Na2SO4 and concentrated under reduced pressure to remove the solvent. Purification by column chromatography (eluent: hexane/EtOAc, 19:1 to 9:1 gradient elution) afforded 2-fluoro-5-cyanobenzenesulfonyl chloride as a yellow oil (569 mg, 71% yield).1H NMR (400 MHz, CDCl3) δ 8.31 (dd, J = 6.2, 2.1 Hz, 1H), 8.04 (dd, J = 8.7, 4.3, 2.1 Hz), 8.04 (ddd, J = 8.7, 4.3, 2.1 Hz). 4.3, 2.1 Hz, 1H), 7.51 (t, J = 8.7 Hz, 1H).LCMS (APCI-) m/z 200 ([M-Cl+O]-, 100%).