N-tert-butylbenzenesulfonamide

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

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

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

Procedure: To a cooled (0° C.) solution of tert-butylamine (42.9 mL, 410.6 mmol) in THF (840 mL) was added dropwise benzenesulfonyl chloride (26.2 mL, 205 mmol) and the reaction mixture was stirred at room temperature under an argon atmosphere for 6 h. The mixture was then filtered and the collected solid washed with THF. The filtrate was concentrated, redissolved in CH2Cl2 and washed with 0.1N HCl and H2O. The organic solution was dried and concentrated to afford the desired product (41.8 g, 95%). The mixture was then filtered the collected solid washed with THF The filtrate was concentrated redissolved in CH2Cl2 washed with 0.1N HCl and H2O The organic solution was dried concentrated

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

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

Procedure: By the method described in Example 10, Step B, N-t-butylbenzenesulfonamide [G. Lombardino, J. Org. Chem., 36, 1843 (1971)] was deprotonated with n-butyllithium, and the resulting dianion was reacted with triisopropyl borate and worked up with acid to give the title compound, which was used directly in the next step without further purification.

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

Procedure: By the method described in Example 10, Step B, N-t-butylbenzenesulfonamide [G. Lombardino, J. Org. Chem., 36, 1843 (1971)] was deprotonated with n-butyllithium, and the resulting dianion was reacted with triisopropyl borate and worked up with acid to give the title compound, which was used directly in the next step without further purification.

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 27 ml of n-butyllithium (15% solution in n-hexane) are added dropwise at −5° C. to a solution of 4.29 g of N-tert-butylbenzenesulfonamide in 25 ml of THF under argon. The mixture is stirred at 22° C. for 1 h, re-cooled to −5° C., and 2.8 g of trimethyl borate are slowly added dropwise. The mixture is stirred at 22° C. for 3 h, before 100 ml of aqueous ammonium chloride solution is added dropwise. The phases are separated, and the aqueous phase is extracted a further twice with MTB ether. The combined organic phases are dried over magnesium sulfate. Filtered and evaporated to dryness in vacuo. re-cooled to −5° C. is added dropwise The phases are separated the aqueous phase is extracted a further twice with MTB ether The combined organic phases are dried over magnesium sulfate Filtered evaporated to dryness in vacuo

Conditions: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 27 ml of n-butyllithium (15% solution in n-hexane) are added dropwise at −5° C. to a solution of 4.29 g of N-tert-butylbenzenesulfonamide in 25 ml of THF under argon. The mixture is stirred at 22° C. for 1 h, re-cooled to −5° C., and 2.8 g of trimethyl borate are slowly added dropwise. The mixture is stirred at 22° C. for 3 h, before 100 ml of aqueous ammonium chloride solution is added dropwise. The phases are separated, and the aqueous phase is extracted a further twice with MTB ether. The combined organic phases are dried over magnesium sulfate. Filtered and evaporated to dryness in vacuo. re-cooled to −5° C. is added dropwise The phases are separated the aqueous phase is extracted a further twice with MTB ether The combined organic phases are dried over magnesium sulfate Filtered evaporated to dryness in vacuo

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

Procedure: A solution of N-(1,1-dimethylethyl)benzenesulfonamide (40.0 g) in 550 ml dry tetrahydrofuran was cooled to 0° and 250 ml of 1.6M n-butyllithium added dropwise at 0°. After the addition of one equivalent of base, the solution turned yellow. After stirring for 2 hours at room temperature, the resulting suspension was cooled to 0° and 13 ml of ethylene oxide added dropwise. After stirring for 3.5 hours at room temperature, the homogeneous yellow solution was poured into water. The product was extracted with ether and dried (Na2SO4). Concentration gave a yellow oil which was purified by column chromatography [400 g silica gel, ether/hexane (1:1) followed by ethyl acetate]. Pure 2-(2-hydroxyethyl)-N-(1,1-dimethylethyl)benzenesulfonamide was obtained as a colorless oil which solidified after several days; m.p. 43°-45°. the resulting suspension was cooled to 0° After stirring for 3.5 hours at room temperature The product was extracted with ether dried (Na2SO4) Concentration gave a yellow oil which was purified by column chromatography [400 g silica gel, ether/hexane (1:1) followed by ethyl acetate]

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

Procedure: To a solution of N-(tert-butyl)benzenesulfonamide (569 mg, 0.00267 mol) in ether (10 mL, 0.1 mol) was added 1.7 M of tert-butyllithium in pentane (4.7 mL) under nitrogen at −78° C. The mixture was stirred at −78° C. for 15 minutes, then at 0° C. for 1 hour. The reaction mixture then was cooled down to −78° C. again and a solution of 1-{[1-(4-chlorophenyl)cyclopropyl]carbonyl}pyrrolidin-3-one (640 mg, 0.0024 mol) in ether was added. After stirring for 2 hours, the reaction mixture was quenched with saturated NH4Cl aqueous solution and then extracted with EtOAc. The combined organic layer was washed with brine, dried over MgSO4 and concentrated. The crude product was purified using Combiflash eluting with 30% AcOEt in hexanes to afford the desired product. LC/MS (M+H+) 478.0. at 0° C. for 1 hour The reaction mixture then was cooled down to −78° C. again After stirring for 2 hours the reaction mixture was quenched with saturated NH4Cl aqueous solution extracted with EtOAc The combined organic layer was washed with brine dried over MgSO4 concentrated The crude product was purified eluting with 30% AcOEt in hexanes

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

Procedure: To a solution of N-(tert-butyl)benzenesulfonamide (536 mg, 0.00251 mol) in ether (10 mL, 0.1 mol) was added 1.7 M of tert-butyllithium in pentane (4.4 mL) under nitrogen at −78° C. The mixture was stirred at −78 Celsius for 15 min, then at 0 Celsius for 1 hour, and then cooled down to −78 Celsius again. A solution of 1-benzylpyrrolidin-3-one (400.0 mg, 0.002283 mol) in ether (3 mL) was added to the above solution. The reaction solution was stirred at −78 Celsius for 2 hours, then quenched with saturated NH4Cl aqueous solution, and then extracted with EtOAc. The organic phase was washed with brine, then dried over MgSO4. The residue was purified by flash chromatography on silica gel column with 30% AcOEt in hexanes to give the desired compound (350 mg, 39% yield). MS (ESI): 389.1 (M+H+). at 0 Celsius for 1 hour cooled down to −78 Celsius again The reaction solution was stirred at −78 Celsius for 2 hours quenched with saturated NH4Cl aqueous solution extracted with EtOAc The organic phase was washed with brine dried over MgSO4 The residue was purified by flash chromatography on silica gel column with 30% AcOEt in hexanes

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

Procedure: To a solution of benzenesulfonyl chloride (722 μL, 0.00566 mol), potassium carbonate (0.939 g, 0.00679 mol) in acetonitrile (15 mL, 0.29 mol) was added tert-butylamine (0.652 mL, 0.00623 mol). The resulting mixture was stirred at r.t. for 30 minutes, followed by filtration and concentration. The resulting residue was diluted with ethyl acetate, and the resulting solution was washed with water then with brine, then dried with MgSO4 followed by concentration. The crude material was purified by flash chromatography on silica gel with 40% AcOEt in hexanes to give the desired compound (1.21 g, 85% yield). MS (ESI): 236.0 (M+Na+). followed by filtration and concentration The resulting residue was diluted with ethyl acetate the resulting solution was washed with water with brine, then dried with MgSO4 followed by concentration The crude material was purified by flash chromatography on silica gel with 40% AcOEt in hexanes