* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
A. Synthesis of (tert-butyl)[(5-chloro(2-thienyl))sulfonyl]amine (0316) A solution of 5.5 g (27.5 mmol) of 5-chlorothiophenesulfonyl chloride in dry THF at 0°C was treated with a solution of 5.7 mL (75.5 mmol) oft-butylamine. After warming to 23°C, the reaction mixture was diluted with 125 mL of diethyl ether, filtered, and washed with 1 N HCl, brine, and dried (MgSO4). Concentration in vacuo affords 6.4 g (98percent) of the named compound as an oil.
A. Synthesis of (tert-butyl)[(5-chloro(2-thienyl))sulfonyl]amine (0316) A solution of 5.5 g (27.5 mmol) of 5-chlorothiophenesulfonyl chloride in dry THF at 0C was treated with a solution of 5.7 mL (75.5 mmol) oft-butylamine. After warming to 23C, the reaction mixture was diluted with 125 mL of diethyl ether, filtered, and washed with 1 N HCl, brine, and dried (MgSO4). Concentration in vacuo affords 6.4 g (98%) of the named compound as an oil.
In tetrahydrofuran; diethyl ether;
A. Synthesis of (tert-butyl)[(5-chloro(2-thienyl))sulfonyl]amine A solution of 5.5 g (27.5 mmol) of 5-chlorothiophenesulfonyl chloride in dry THF at 0 C. was treated with a solution of 5.7 mL (75.5 mmol) of t-butylamine. After warning to 23 C., the reaction mixture was diluted with 125 mL of diethyl ether, filtered, and washed with 1 N HCl, brine, and dried (MgSO4). Concentration in vacuo affords 6.4 g (98%) of the named compound as an oil.
In tetrahydrofuran; diethyl ether;
A. Synthesis of (tert-butyl)[(5-chloro(2-thienyl))sulfonyl]amine A solution of 5.5 g (27.5 mmol) of 5-chlorothiophenesulfonyl chloride in dry THF at 0 C. was treated with a solution of 5.7 mL (75.5 mmol) of t-butylamine. After warning to 23 C., the reaction mixture was diluted with 125 mL of diethyl ether, filtered, and washed with 1 N HCl, brine, and dried (MgSO4). Concentration in vacuo affords 6.4 g (98%) of the named compound as an oil.
A solution of Example 311A (1.01 g, 3.99 mmol) in tetrahydrofuran (32 ML) at -78 C. was treated with dropwise addition of sec-BuLi (1.4 M in hexane, 2.1 equivalents).The reaction was warmed to -20 C. and stirred for 30 minutes, treated with a solution of tosyl azide (1.1 equivalent) in tetrahydrofuran (7 ML) at -20 C., stirred at 25 C. for 18 hours.The reaction mixture was quenched with water and extracted with ethyl acetate.The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated.The residue was purified by column chromatography on silica gel, eluding with a gradient of 30% dichloromethane in hexane to 100% dichloromethane to give approximately a 2:1 mixture of starting material to the title compound.
B. Synthesis of (tert-butyl)[(5-chloro-3-fluoro(2-thienyl))sulfonyl]amine A THF solution (1.5 mL) of 128 mg (0.50 mmol) of <strong>[155731-14-9](tert-butyl)[(5-chloro(2-thienyl))sulfonyl]amine</strong> was cooled to -78 C. and treated with 954 muL (1.5 mmol) of a 1.6 M solution of butyl lithium in hexane. After 1 h, 159 mg (0.5 mmol) of bis(phenylsulfonyl)fluoroamine was added and the solution was allowed to warm to 23 C. The reaction was quenched with 1 mL of sat. NH4Cl, extracted 3 times with diethyl ether, dried (MgSO4), concentrated in vacuo to afford a quantitative yield (147 mg) of the desire product. 19F-NMR (CDCl3) delta(ppm): -113.4.
With n-butyllithium; In hexane;
B. Synthesis of (tert-butyl)[(5-chloro-3-fluoro(2-thienyl))sulfonyl]amine A THF solution (1.5 mL) of 128 mg (0.50 mmol) of <strong>[155731-14-9](tert-butyl)[(5-chloro(2-thienyl))sulfonyl]amine</strong> was cooled to -78 C. and treated with 954 muL (1.5 mmol) of a 1.6 M solution of butyl lithium in hexane. After 1 h, 159 mg (0.5 mmol) of bis(phenylsulfonyl)fluoroamine was added and the solution was allowed to warm to 23 C. The reaction was quenched with 1 mL of sat. NH4Cl, extracted 3 times with diethyl ether, dried (MgSO4), concentrated in vacuo to afford a quantitative yield (147 mg) of the desire product. 19F-NMR (CDCl3) delta (ppm): -113.4.
With n-butyllithium; sodium borohydrid; In tetrahydrofuran; hexane; water; ethyl acetate;
a 3-Amino-<strong>[155731-14-9]5-chlorothiophene-2-sulfonic acid tert-butylamide</strong> A solution of 38.1 g (0.15 mol) of <strong>[155731-14-9]5-chlorothiophene-2-sulfonic acid tert-butylamide</strong> in 300 ml of dry tetrahydrofuran was cooled to -70 C, and n-BuLi (190 ml, 1.6M in hexane) was added, maintaining the temperature <-65 C. After addition, the mixture was allowed to warm to -20 C. and stirred at this temperature for 30 min. A solution of p-toluenesulfonyl azide (34 g, 0.17 mol) in 100 ml of dry tetrahydrofuran was added, maintaining the temperature at -20 C., and the cooling bath was removed. After the mixture had reached room temperature, water (100 ml) was added. The organic phase was isolated and the aqueous phase was extracted with toluene (2*50 ml). To the combined organic phases was added hexadecyltributylphosphonium bromide (7.62 g, 15 mmol) followed by the dropwise addition of a solution of sodium borohydride (6.58 g, 0.174 mol) in 20 ml of water with stirring and cooling to room temperature. The mixture was stirred over night at room temperature, and water (100 ml) was added. The organic phase was isolated, washed with water (2*100 ml), dried, and evaporated to dryness. The oily residue was dissolved in ethyl acetate (150 ml) and washed with 1N sodium hydroxide (6*100 ml). The organic phase was dried with sodium sulfate, and evaporated to afford a quantitative yield (40.6 g) of crude title compound as an oil, which was used without further purification in the next step.
With sec-BuLi; In tetrahydrofuran; hexane; dichloromethane;
Example 311B 3-azido-<strong>[155731-14-9]N-(tert-butyl)-5-chlorothiophene-2-sulfonamide</strong> A solution of Example 311A (1.01 g, 3.99 mmol) in tetrahydrofuran (32 mL) at -78 C. was treated with dropwise addition of sec-BuLi (1.4 M in hexane, 2.1 equivalents). The reaction was warmed to -20 C. and stirred for 30 minutes, treated with a solution of tosyl azide (1.1 equivalent) in tetrahydrofuran (7 mL) at -20 C., stirred at 25 C. for 18 hours. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel, eluding with a gradient of 30% dichloromethane in hexane to 100% dichloromethane to give approximately a 2:1 mixture of starting material to the title compound.
B. Synthesis of (tert-butyl)[(5-chloro-3-fluoro(2-thienyl))sulfonyl]amine (0317) A THF solution (1.5 mL) of 128 mg (0.50 mmol) of <strong>[155731-14-9](tert-butyl)[(5-chloro(2-thienyl))sulfonyl]amine</strong> was cooled to -78C and treated with 954 muL (1.5 mmol) of a 1.6 M solution of butyl lithium in hexane. After 1 h, 159 mg (0.5 mmol) of bis(phenylsulfonyl)fluoroamine was added and the solution was allowed to warm to 23 C. The reaction was quenched with 1 mL of sat. NH4Cl, extracted 3 times with diethyl ether, dried (MgSO4), concentrated in vacuo to afford a quantitative yield (147 mg) of the desire product. 19F-NMR (CDCl3) delta (ppm): -113.4.