4-fluorobenzenesulfonyl fluoride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of compound 4-Fluorobenzenesulfonyl chloride (50 g, 0.256 mol) in ACN (500 mL) was added KF (74.36 g, 5 eq) and 18-crown-6 (2 g) at r.t., then the mixture was stirred at r.t. overnight. The mixture was detected by LC-MS, then saturated aqueous NaHCO3 was added and the mixture was extracted with EtOAc, the organic layer was washed with saturated aqueous NaHCO3, brine, dried over anhydrous Na2SO4, concentrated to give the crude compound 4-Fluorobenzenesulfonyl fluoride (46.70 g) as pale yellow oil which was used for the next step without further purification. ESI-MS (M+1): 179 calc. for C6H4F2O2S. the mixture was extracted with EtOAc the organic layer was washed with saturated aqueous NaHCO3, brine dried over anhydrous Na2SO4 concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of compound 4-Fluorobenzenesulfonyl chloride (50 g, 0.256 mol) in ACN (500 mL) was added KF (74.36 g, 5 eq) and 18-crown-6 (2 g) at r.t., then the mixture was stirred at r.t. overnight. The mixture was detected by LC-MS, then saturated aqueous NaHCO3 was added and the mixture was extracted with EtOAc, the organic layer was washed with saturated aqueous NaHCO3, brine, dried over anhydrous Na2SO4, concentrated to give the crude compound 4-Fluorobenzenesulfonyl fluoride (46.70 g) as pale yellow oil which was used for the next step without further purification. ESI-MS (M+1): 179 calc. for C6H4F2O2S. the mixture was extracted with EtOAc the organic layer was washed with saturated aqueous NaHCO3, brine dried over anhydrous Na2SO4 concentrated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-indole carboxylic acid tert-butyl ester (1.88 g, 8.65 mmol) in 100 mL of anhydrous THF was cooled to −78° C. in a dry ice/acetone bath under an argon gas blanket. A fresh commercial (Aldrich) 1.7 M solution of t-BuLi in pentane (10.2 mL, 17.3 mmol, 2.0 eq) was slowly added to the stirring mixture via syringe. During the addition, the solution turned from a light amber-red color to a dark, orange-burgundy color. After the addition was complete, the reaction mixture was allowed to stir for 45 minutes at −78° C. and then 4-fluorobenzenesulfonyl fluoride was slowly added to the reaction mixture while carefully maintaining an internal temperature of <−65° C. The reaction mixture was kept at −75 to −78° C. for a period of 20 minutes after the addition was complete then was allowed to warm to room temperature, where it remained for 2 h. The reaction mixture was poured into 500 mL of saturated NH4Cl solution, diluted with 500 mL of EtOAc and mixed well. The pale, amber-orange organic layer was separated, washed with brine and dried over anhydrous magnesium sulfate. Evaporation of the solvent gave a dark amber oil which was silica-gel chromatographed, gradient eluting with 10% EtOAc/Hexane followed by CHCl3 to give 1.40 g, 3.73 mmol, 43.1% yield of the 2-(4-Fluoro-benzenesulfonyl)-indole-1-carboxylic acid tert-butyl ester as an amber oil which solidified on standing to a pale reddish-tan solid which had a melting point range of 88–93° C. During the addition After the addition while carefully maintaining an internal temperature of <−65° C The reaction mixture was kept at −75 to −78° C. for a period of 20 minutes after the addition to warm to room temperature where it remained for 2 h mixed well The pale, amber-orange organic layer was separated washed with brine dried over anhydrous magnesium sulfate Evaporation of the solvent gave a dark amber oil which chromatographed gradient eluting with 10% EtOAc/Hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of compound 4-Fluorobenzenesulfonyl chloride (50 g, 0.256 mol) in ACN (500 mL) was added KF (74.36 g, 5 eq) and 18-crown-6 (2 g) at r.t., then the mixture was stirred at r.t. overnight. The mixture was detected by LC-MS, then saturated aqueous NaHCO3 was added and the mixture was extracted with EtOAc, the organic layer was washed with saturated aqueous NaHCO3, brine, dried over anhydrous Na2SO4, concentrated to give the crude compound 4-Fluorobenzenesulfonyl fluoride (46.70 g) as pale yellow oil which was used for the next step without further purification. ESI-MS (M+1): 179 calc. for C6H4F2O2S. the mixture was extracted with EtOAc the organic layer was washed with saturated aqueous NaHCO3, brine dried over anhydrous Na2SO4 concentrated