benzenesulfonyl fluoride

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a −75° C. solution of 4-(1-methyl-1H-indol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester compound 3-1 (330 mg, 1.05 mmol) in THF (25 mL) was slowly added t-BuLi (1.2 mL, 2.1 mmol). The reaction mixture was stirred for 30 minutes at −75° C. then warmed in an ice bath for 15 min. The reaction was re-cooled to −75° C. and benzenesulfonyl fluoride was added (0.2 mL, 1.6 mmol). The reaction was stirred cold for 1.5 h at which time the ice bath was removed and the reaction was allowed to warm to room temperature (45 min.). The reaction was quenched with a saturated solution of ammonium chloride (55 mL) and extracted with ethyl acetate (3×20 mL). The combined ethyl acetate layers were washed with brine (25 mL), dried (MgSO4), filtered and concentrated to afford a yellow oil. The oil was chromatographed over silica eluting with hexanes/ethyl acetate (4:1) to afford 190 mg (40%) of 4-(2-benzenesulfonyl-1-methyl-1H-indol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (3-2). To a −75° C. then warmed in an ice bath for 15 min The reaction was re-cooled to −75° C. was removed to warm to room temperature (45 min.) The reaction was quenched with a saturated solution of ammonium chloride (55 mL) extracted with ethyl acetate (3×20 mL) The combined ethyl acetate layers were washed with brine (25 mL) dried (MgSO4) filtered concentrated to afford a yellow oil The oil was chromatographed over silica eluting with hexanes/ethyl acetate (4:1)

Conditions: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a −75° C. solution of 4-(1-methyl-1H-indol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester compound 3-1 (330 mg, 1.05 mmol) in THF (25 mL) was slowly added t-BuLi (1.2 mL, 2.1 mmol). The reaction mixture was stirred for 30 minutes at −75° C. then warmed in an ice bath for 15 min. The reaction was re-cooled to −75° C. and benzenesulfonyl fluoride was added (0.2 mL, 1.6 mmol). The reaction was stirred cold for 1.5 h at which time the ice bath was removed and the reaction was allowed to warm to room temperature (45 min.). The reaction was quenched with a saturated solution of ammonium chloride (55 mL) and extracted with ethyl acetate (3×20 mL). The combined ethyl acetate layers were washed with brine (25 mL), dried (MgSO4), filtered and concentrated to afford a yellow oil. The oil was chromatographed over silica eluting with hexanes/ethyl acetate (4:1) to afford 190 mg (40%) of 4-(2-benzenesulfonyl-1-methyl-1H-indol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (3-2). To a −75° C. then warmed in an ice bath for 15 min The reaction was re-cooled to −75° C. was removed to warm to room temperature (45 min.) The reaction was quenched with a saturated solution of ammonium chloride (55 mL) extracted with ethyl acetate (3×20 mL) The combined ethyl acetate layers were washed with brine (25 mL) dried (MgSO4) filtered concentrated to afford a yellow oil The oil was chromatographed over silica eluting with hexanes/ethyl acetate (4:1)

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

Procedure: BuLi (2.2 M solution in Et2O. 2.4 mL, 5.4 mmol) was slowly added to a solution of 6-bromo-5-fluoro-3,3-dimethyl-1-triisopropylsilanyl-2,3-dihydro-1H-indole (1.8 g, 4.5 mmol) in THF (20 mL) at −78° C. under nitrogen. The solution was stirred for 15 minutes at −78° C. and then phenylsulfonyl fluoride (541 μL, 4.5 mmol) was slowly added. Stirring was maintained for 1 h at the same temperature. The reaction was quenched by adding saturated aqueous NH4Cl and the product was extracted with EtOAc. The organic phase was dried (MgSO4), filtered and concentrated. The crude material was purified by SiO2 chromatography (10% EtOAc in petrol) to give the title compound (1.4 g) as a yellow solid. 1H NMR (CDCl3): 7.98 (2H, d), 7.64-7.56 (1H, m), 7.56-7.48 (2H, m), 7.23 (1H, d), 6.68 (1H, d), 3.50 (2H, s), 1.55-1.45 (3H, m), 1.24 (6H, s), 1.21-1.11 (18H, m). Stirring was maintained for 1 h at the same temperature The reaction was quenched by adding saturated aqueous NH4Cl the product was extracted with EtOAc The organic phase was dried (MgSO4) filtered concentrated The crude material was purified by SiO2 chromatography (10% EtOAc in petrol)

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

Procedure: To as stirred solution of 6-bromo-1-triisopropylsilanyl-1H-indole (0.687 g, 1.95 mmol) in THF (12 mL) at −78° C. under nitrogen was added, dropwise over 0.3 h, a solution of tert-butyllithium in pentane (1.7 M, 2.52 mL, 4.29 mmol) (internal temperature was kept below −70° C.). The mixture was stirred at −78° C. for 0.1 h then phenylsulfonyl fluoride (0.26 mL, 0.343 g, 2.15 mmol) was added dropwise. The mixture was stirred at −78° C. then warmed to 20° C. and stirred thus for 1 h. Excess tert-butyllithium was quenched by addition of ice and the resulting mixture was partitioned between water (100 mL) and EtOAc (3×50 mL). The combined organic extracts were dried (Na2SO4) and evaporated in vacuo to give semi-solid. Chromatography (SiO2; gradient elution with 0-40% Et2O in petrol) gave the title compound (0.365 g, 45%). 1H NMR (CDCl3): 8.21 (1H, s), 8.00-7.89 (2H, m), 7.70 (1H, d), 7.63 (1H, dd), 7.57-7.41 (4H, m), 6.69 (1H, d), 1.82-1.65 (3H, m), 1.16 (18H, d). was added, dropwise over 0.3 h The mixture was stirred at −78° C. then warmed to 20° C. stirred thus for 1 h Excess tert-butyllithium was quenched by addition of ice the resulting mixture was partitioned between water (100 mL) and EtOAc (3×50 mL) The combined organic extracts were dried (Na2SO4) evaporated in vacuo to give semi-solid Chromatography (SiO2; gradient elution with 0-40% Et2O in petrol)

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

Procedure: Cool a solution of 5-bromo-1-triisopropylsilanyl-1H-indole (9 g, 25.5 mmol) in 550 mL anhydrous THF to −75° C. under argon and treat with 1.7 M t-butyl lithium (33 mL, 56.2 mmol) while keeping the temperature below −60° C. After the addition, recool the reaction mixture to about −73° C. before adding a solution of phenylsulfonyl fluoride (4.6 g, 28.7 mmol) in 30 mL THF. Stir the reaction at −78° C. for 1 hour then quench with saturated NaHCO3 followed by brine. Separate the layers and extract the aqueous layer with EtOAc. Treat the combined organic layers with 1 M tetrabutylammonium fluoride (35 mL) in THF for 1 hour at ambient temperature, then concentrate to dryness. Combine the residue with EtOAc, wash twice with 1 N HCl, dry over MgSO4, and concentrate to an oil. Chromatograph the oil on silica get eluting stepwise with 50% CHCl3 in hexanes followed by 50% CHC13 in MeOH give an oily solid. Triturate the oily solid with CHCl3 to give the title compound as a solid: Analysis for C14H11NO2S H2O: calcd: C, 64.89; H, 4.36; N, 5.41; found: C, 64.76; H, 4.45; N, 5.33; ISMS 257 (M+). the temperature below −60° C After the addition to about −73° C. the reaction at −78° C. for 1 hour then quench with saturated NaHCO3 Separate the layers extract the aqueous layer with EtOAc Treat the combined organic layers with 1 M tetrabutylammonium fluoride (35 mL) in THF for 1 hour at ambient temperature concentrate to dryness Combine the residue with EtOAc, wash twice with 1 N HCl dry over MgSO4 concentrate to an oil Chromatograph the oil on silica get eluting stepwise with 50% CHCl3 in hexanes give an oily solid Triturate the oily solid with CHCl3

Conditions: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a −75° C. solution of 4-(1-methyl-1H-indol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester compound 3-1 (330 mg, 1.05 mmol) in THF (25 mL) was slowly added t-BuLi (1.2 mL, 2.1 mmol). The reaction mixture was stirred for 30 minutes at −75° C. then warmed in an ice bath for 15 min. The reaction was re-cooled to −75° C. and benzenesulfonyl fluoride was added (0.2 mL, 1.6 mmol). The reaction was stirred cold for 1.5 h at which time the ice bath was removed and the reaction was allowed to warm to room temperature (45 min.). The reaction was quenched with a saturated solution of ammonium chloride (55 mL) and extracted with ethyl acetate (3×20 mL). The combined ethyl acetate layers were washed with brine (25 mL), dried (MgSO4), filtered and concentrated to afford a yellow oil. The oil was chromatographed over silica eluting with hexanes/ethyl acetate (4:1) to afford 190 mg (40%) of 4-(2-benzenesulfonyl-1-methyl-1H-indol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (3-2). To a −75° C. then warmed in an ice bath for 15 min The reaction was re-cooled to −75° C. was removed to warm to room temperature (45 min.) The reaction was quenched with a saturated solution of ammonium chloride (55 mL) extracted with ethyl acetate (3×20 mL) The combined ethyl acetate layers were washed with brine (25 mL) dried (MgSO4) filtered concentrated to afford a yellow oil The oil was chromatographed over silica eluting with hexanes/ethyl acetate (4:1)