O-(2-trimethylsilylethyl)hydroxylamine;hydrochloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-methyl-2-(5-pyridin-2-ylthiophene-2-sulfonylamino)-propionic acid (1.60 grams, 4.91 mmole) in methylene chloride (160 mL) was added triethylamine (2.3 mL, 16.5 mmole), (benzotriazol-1-yloxy)tris(dimethylamino)-phosphonium hexafluorophosphate (2.4 grams, 5.41 mmole) and O-(2-trimethylsilylethyl)hydroxylamine hydrochloride (0.92 grams, 5.41 mmole). The resulting mixture was stirred at room temperature for 16 hours. The solvent was evaporated and the residue was taken up in ethyl acetate. The solution was washed with water, aqueous saturated sodium bicarbonate solution, and brine. After drying over magnesium sulfate, the solvent was evaporated to afford a white foam from which the desired product, 2-methyl-2-(5-pyridin-2-ylthiophene-2-sulfonylamino)-N-(2-trimethylsilanylethoxy)-propionamide (220 mg, 10%), a white solid, was isolated by chromatography on silica gel eluting with 3:2 ethyl acetate/hexanes. The solvent was evaporated The solution was washed with water, aqueous saturated sodium bicarbonate solution, and brine After drying over magnesium sulfate the solvent was evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (4R)-l -[4-(4-fluorophenoxy)benzyl]-2-oxo-imidazolidine-4-carboxylic acid (120 mg, 0.36 mmol) in methylene chloride (5 mL) were added sequentially 1-hydroxybenztria zole (73 mg, 0.54 mmol), diisopropylethylamine (0.13 mL, 0.75 mmol), O-(2-trimethylsilylethyl)hydroxylamine hydrochloride (92 mg, 0.54 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (104 mg, 0.54 mmol). The reaction mixture was stirred at room temperature for 16 hours and was then diluted with methylene chloride and water. The organic phase was washed successively with aqueous 1M HCI solution, water, aqueous saturated NaHCO3 solution and brine. After drying over MgSO4, the solution was concentrated to an oil. The title compound, an oil (85 mg, 53%), was isolated by chromatography on silica gel eluting with ethyl acetate. The organic phase was washed successively with aqueous 1M HCI solution, water, aqueous saturated NaHCO3 solution and brine After drying over MgSO4 the solution was concentrated to an oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-methyl-2-(5-pyridin-2-ylthiophene-2-sulfonylamino)-propionic acid (1.60 grams, 4.91 mmole) in methylene chloride (160 mL) was added triethylamine (2.3 mL, 16.5 mmole), (benzotriazol-1-yloxy)tris(dimethylamino)-phosphonium hexafluorophosphate (2.4 grams, 5.41 mmole) and O-(2-trimethylsilylethyl)hydroxylamine hydrochloride (0.92 grams, 5.41 mmole). The resulting mixture was stirred at room temperature for 16 hours. The solvent was evaporated and the residue was taken up in ethyl acetate. The solution was washed with water, aqueous saturated sodium bicarbonate solution, and brine. After drying over magnesium sulfate, the solvent was evaporated to afford a white foam from which the desired product, 2-methyl-2-(5-pyridin-2-ylthiophene-2-sulfonylamino)-N-(2-trimethylsilanylethoxy)-propionamide (220 mg, 10%), a white solid, was isolated by chromatography on silica gel eluting with 3:2 ethyl acetate/hexanes. The solvent was evaporated The solution was washed with water, aqueous saturated sodium bicarbonate solution, and brine After drying over magnesium sulfate the solvent was evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-methyl-2-(5-pyridin-2-ylthiophene-2-sulfonylamino)-propionic acid (1.60 grams, 4.91 mmole) in methylene chloride (160 mL) was added triethylamine (2.3 mL, 16.5 mmole), (benzotriazol-1-yloxy)tris(dimethylamino)-phosphonium hexafluorophosphate (2.4 grams, 5.41 mmole) and O-(2-trimethylsilylethyl)hydroxylamine hydrochloride (0.92 grams, 5.41 mmole). The resulting mixture was stirred at room temperature for 16 hours. The solvent was evaporated and the residue was taken up in ethyl acetate. The solution was washed with water, aqueous saturated sodium bicarbonate solution, and brine. After drying over magnesium sulfate, the solvent was evaporated to afford a white foam from which the desired product, 2-methyl-2-(5-pyridin-2-ylthiophene-2-sulfonylamino)-N-(2-trimethylsilanylethoxy)-propionamide (220 mg, 10%), a white solid, was isolated by chromatography on silica gel eluting with 3:2 ethyl acetate/hexanes. The solvent was evaporated The solution was washed with water, aqueous saturated sodium bicarbonate solution, and brine After drying over magnesium sulfate the solvent was evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (2R, 4S)-4-(4-benzyloxyphenyl)-5-oxo-pyrrolidine-2-carboxylic acid (330 mg, 1.06 mmol), N-methyl morpholine (0.25 mL, 2.3 mmol) and O-(2-trimethylsilylethyl) hydroxylamine hydrochloride (220 mg, 1.30 mmol) in CH2Cl2 (20 mL) was added (benztriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluoroborate (560 mg, 1.27 mmol). The reaction was stirred at room temperature for 6 hours. After dilution with CH2Cl2, the mixture was washed sequentially with aqueous 0.5M HCl solution, water, aqueous saturated NaHCO3 solution, and brine. The solution was dried over MgSO4 and concentrated to a white solid that was triturated with ethyl acetate and set aside. The trituration filtrate was concentrated and chromatographed on silica gel eluting with 5% methanol in chloroform. Fractions containing the title compound were combined and concentrated to afford a white solid that was combined with the solid obtained directly from the crude product mixture. The sample was stirred in water overnight. The title compound was collected by filtration and dried. The yield was 194 mg (43%). After dilution with CH2Cl2, the mixture was washed sequentially with aqueous 0.5M HCl solution, water, aqueous saturated NaHCO3 solution, and brine The solution was dried over MgSO4 concentrated to a white solid that was triturated with ethyl acetate The trituration filtrate was concentrated chromatographed on silica gel eluting with 5% methanol in chloroform Fractions containing the title compound concentrated to afford a white solid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (4R)-l -[4-(4-fluorophenoxy)benzyl]-2-oxo-imidazolidine-4-carboxylic acid (120 mg, 0.36 mmol) in methylene chloride (5 mL) were added sequentially 1-hydroxybenztria zole (73 mg, 0.54 mmol), diisopropylethylamine (0.13 mL, 0.75 mmol), O-(2-trimethylsilylethyl)hydroxylamine hydrochloride (92 mg, 0.54 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (104 mg, 0.54 mmol). The reaction mixture was stirred at room temperature for 16 hours and was then diluted with methylene chloride and water. The organic phase was washed successively with aqueous 1M HCI solution, water, aqueous saturated NaHCO3 solution and brine. After drying over MgSO4, the solution was concentrated to an oil. The title compound, an oil (85 mg, 53%), was isolated by chromatography on silica gel eluting with ethyl acetate. The organic phase was washed successively with aqueous 1M HCI solution, water, aqueous saturated NaHCO3 solution and brine After drying over MgSO4 the solution was concentrated to an oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-methyl-2-(5-pyridin-2-ylthiophene-2-sulfonylamino)-propionic acid (1.60 grams, 4.91 mmole) in methylene chloride (160 mL) was added triethylamine (2.3 mL, 16.5 mmole), (benzotriazol-1-yloxy)tris(dimethylamino)-phosphonium hexafluorophosphate (2.4 grams, 5.41 mmole) and O-(2-trimethylsilylethyl)hydroxylamine hydrochloride (0.92 grams, 5.41 mmole). The resulting mixture was stirred at room temperature for 16 hours. The solvent was evaporated and the residue was taken up in ethyl acetate. The solution was washed with water, aqueous saturated sodium bicarbonate solution, and brine. After drying over magnesium sulfate, the solvent was evaporated to afford a white foam from which the desired product, 2-methyl-2-(5-pyridin-2-ylthiophene-2-sulfonylamino)-N-(2-trimethylsilanylethoxy)-propionamide (220 mg, 10%), a white solid, was isolated by chromatography on silica gel eluting with 3:2 ethyl acetate/hexanes. The solvent was evaporated The solution was washed with water, aqueous saturated sodium bicarbonate solution, and brine After drying over magnesium sulfate the solvent was evaporated