Uses
4-Chloro-2-fluorobenzenesulfonyl chloride (4-chloro-2-fluorobenzene-1-sulfonyl chloride) may be used to synthesize [1-(4-chloro-2-fluorophenylsulfonyl) piperidin-4-yl] diphenylmethanol.
Synthesis
General procedure for the synthesis of 4-chloro-2-fluorobenzenesulfonyl chloride from 4-chloro-2-fluoroaniline:
1. 4-Chloro-2-fluoroaniline (22.90 g, 151 mmol) was dissolved in 120 mL of acetic acid and 80 mL of concentrated hydrochloric acid was added with stirring.
2. the reaction mixture was cooled to 0 °C and a solution of sodium nitrite (27.2 g, 0.4 mol) dissolved in 40 mL of water was added over 10 minutes.
3. The reaction mixture was stirred at 0 °C for 30 min.
4. in another flask, cuprous chloride (500 mg) was dissolved in 200 mL of acetic acid.
5. The flask was cooled to 0 °C and sulfur dioxide gas was passed into the solution for 40 min.
6. The diazonium salt solution prepared in step 3 was slowly added to the solution containing cuprous chloride and sulfur dioxide over a period of 20 minutes, at which time vigorous gas escape was observed.
7. After the addition, the ice bath is removed and the reaction mixture is allowed to gradually warm to room temperature.
8. The reaction mixture was poured into 500 g of crushed ice and the precipitated solid product was collected, washed and dried to give 26.1 g (73% yield) of 4-chloro-2-fluorobenzenesulfonyl chloride.
References
[1] Patent: US2003/232859, 2003, A1. Location in patent: Page 56
[2] Journal of Medicinal Chemistry, 2014, vol. 57, # 22, p. 9539 - 9553
