4-(((tert-butyldiMethylsilyl)oxy)Methyl)aniline

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a suspension of 7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.6 g, 2.1 mmol) in tetrahydrofuran (10 ml) were added oxalyl chloride (0.33 ml, 4.3 mmol) and N,N-dimethylformamide (1 drop) at 0° C., and the mixture was stirred at room temperature for 2.5 hours. The solvent was evaporated, and the residue was dissolved in tetrahydrofuran (6 ml). To the mixture was dropwise added 4-(t-butyldimethylsilyloxymethyl)aniline (0.56 g, 2.4 mmol) and triethylamine (0.36 ml, 2.6 mmol) in tetrahydrofuran (2 ml) at 0° C., and the mixture was stirred at room temperature for 16 hours. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium chloride solution and dried with magnesium sulfate. The solvent was evaporated, and the residue was subjected to silica gel column chromatography. Crude amide (1.1 g) was obtained from fractions of hexane:ethyl acetate=5:1. This product was dissolved in acetone (8 ml), and to the mixture was dropwise added 6N hydrochloric acid. The mixture was stirred for 1 hour. To the mixture were added 1% sodium hydrogen carbonate (100 ml) and diisopropylether (100 ml), and precipitate was filtered, which were dissolved in acetone. The mixture was dried with magnesium sulfate, and the solvent was evaporated. The resulting powder was recrystallized from acetone-diisopropyl-ether to give N-(4-hydroxymethylphenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (0.87 g) as colorless crystals. The solvent was evaporated the residue was dissolved in tetrahydrofuran (6 ml) at 0° C. the mixture was stirred at room temperature for 16 hours the mixture was extracted with ethyl acetate The extract was washed with saturated sodium chloride solution dried with magnesium sulfate The solvent was evaporated Crude amide (1.1 g) was obtained from fractions of hexane The mixture was stirred for 1 hour was filtered which were dissolved in acetone The mixture was dried with magnesium sulfate the solvent was evaporated The resulting powder was recrystallized from acetone-diisopropyl-ether

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

実験手順: To a suspension of 7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.6 g, 2.1 mmol) in tetrahydrofuran (10 ml) were added oxalyl chloride (0.33 ml, 4.3 mmol) and N,N-dimethylformamide (1 drop) at 0° C., and the mixture was stirred at room temperature for 2.5 hours. The solvent was evaporated, and the residue was dissolved in tetrahydrofuran (6 ml). To the mixture was dropwise added 4-(t-butyldimethylsilyloxymethyl)aniline (0.56 g, 2.4 mmol) and triethylamine (0.36 ml, 2.6 mmol) in tetrahydrofuran (2 ml) at 0° C., and the mixture was stirred at room temperature for 16 hours. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium chloride solution and dried with magnesium sulfate. The solvent was evaporated, and the residue was subjected to silica gel column chromatography. Crude amide (1.1 g) was obtained from fractions of hexane:ethyl acetate=5:1. This product was dissolved in acetone (8 ml), and to the mixture was dropwise added 6N hydrochloric acid. The mixture was stirred for 1 hour. To the mixture were added 1% sodium hydrogen carbonate (100 ml) and diisopropylether (100 ml), and precipitate was filtered, which were dissolved in acetone. The mixture was dried with magnesium sulfate, and the solvent was evaporated. The resulting powder was recrystallized from acetone-diisopropyl-ether to give N-(4-hydroxymethylphenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (0.87 g) as colorless crystals. The solvent was evaporated the residue was dissolved in tetrahydrofuran (6 ml) at 0° C. the mixture was stirred at room temperature for 16 hours the mixture was extracted with ethyl acetate The extract was washed with saturated sodium chloride solution dried with magnesium sulfate The solvent was evaporated Crude amide (1.1 g) was obtained from fractions of hexane The mixture was stirred for 1 hour was filtered which were dissolved in acetone The mixture was dried with magnesium sulfate the solvent was evaporated The resulting powder was recrystallized from acetone-diisopropyl-ether

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

実験手順: To a suspension of 7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.6 g, 2.1 mmol) in tetrahydrofuran (10 ml) were added oxalyl chloride (0.33 ml, 4.3 mmol) and N,N-dimethylformamide (1 drop) at 0° C., and the mixture was stirred at room temperature for 2.5 hours. The solvent was evaporated, and the residue was dissolved in tetrahydrofuran (6 ml). To the mixture was dropwise added 4-(tert-butyldimethylsilyloxymethyl)aniline (0.56 g, 2.4 mmol) and triethylamine (0.36 ml, 2.6 mmol) in tetrahydrofuran (2 ml) at 0° C., and the mixture was stirred at room temperature for 16 hours. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium chloride solution and dried with magnesium sulfate. The solvent was evaporated, and the residue was subjected to silica gel column chromatography. Crude amide (1.1 g) was obtained from fractions of hexane:ethyl acetate=5:1. This product was dissolved in acetone (8 ml), and to the mixture was dropwise added 6N hydrochloric acid. The mixture was stirred for 1 hour. To the mixture were added 1% sodium hydrogen carbonate (100 ml) and diisopropylether (100 ml), and precipitate was filtered, which were dissolved in acetone. The mixture was dried with magnesium sulfate, and the solvent was evaporated. The resulting powder was recrystallized from acetone-diisopropyl-ether to give N-(4-hydroxymethylphenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (0.87 g) as colorless crystals. The solvent was evaporated the residue was dissolved in tetrahydrofuran (6 ml) at 0° C. the mixture was stirred at room temperature for 16 hours the mixture was extracted with ethyl acetate The extract was washed with saturated sodium chloride solution dried with magnesium sulfate The solvent was evaporated Crude amide (1.1 g) was obtained from fractions of hexane The mixture was stirred for 1 hour was filtered which were dissolved in acetone The mixture was dried with magnesium sulfate the solvent was evaporated The resulting powder was recrystallized from acetone-diisopropyl-ether

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

実験手順: In ethanol (80 ml) was dissolved tert-butyldimethyl-4-nitrobenzyloxysilane (16.5 g), and to the mixture was added dried 5% palladium on carbon (0.83 g). Under hydrogen atmosphere, the mixture was stirred at room temperature under atmospheric pressure for 7.5 hours. The palladium was filtered off, and the filtrate was concentrated. The residue was separated and purified with column chromatography (ethyl acetate/hexane=1/4) to give 4-aminobenzyloxy-tert-butyldimethylsilane (13.8 g) as colorless oil. to the mixture was added dried 5% palladium on carbon (0.83 g) The palladium was filtered off the filtrate was concentrated The residue was separated purified with column chromatography (ethyl acetate/hexane=1/4)

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a suspension of 7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.6 g, 2.1 mmol) in tetrahydrofuran (10 ml) were added oxalyl chloride (0.33 ml, 4.3 mmol) and N,N-dimethylformamide (1 drop) at 0° C., and the mixture was stirred at room temperature for 2.5 hours. The solvent was evaporated, and the residue was dissolved in tetrahydrofuran (6 ml). To the mixture was dropwise added 4-(tert-butyldimethylsilyloxymethyl)aniline (0.56 g, 2.4 mmol) and triethylamine (0.36 ml, 2.6 mmol) in tetrahydrofuran. (2 ml) at 0° C., and the mixture was stirred at room temperature for 16 hours. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium chloride solution and dried with magnesium sulfate. The solvent was evaporated, and the residue was subjected to silica gel column chromatography. Crude amide (1.1 g) was obtained from fractions of hexane:ethyl acetate=5:1. This product was dissolved in acetone (8 ml), and to the mixture was dropwise added 6N hydrochloric acid. The mixture was stirred for 1 hour. To the mixture were added 1% sodium hydrogen carbonate (100 ml) and diisopropylether (100 ml), and precipitate was filtered, which were dissolved in acetone. The mixture was dried with magnesium sulfate, and the solvent was evaporated. The resulting powder was recrystallized from acetone-diisopropyl-ether to give N-(4-hydroxymethylphenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (0.87 g) as colorless crystals. The solvent was evaporated the residue was dissolved in tetrahydrofuran (6 ml) (2 ml) at 0° C., and the mixture was stirred at room temperature for 16 hours the mixture was extracted with ethyl acetate The extract was washed with saturated sodium chloride solution dried with magnesium sulfate The solvent was evaporated Crude amide (1.1 g) was obtained from fractions of hexane The mixture was stirred for 1 hour was filtered which were dissolved in acetone The mixture was dried with magnesium sulfate the solvent was evaporated The resulting powder was recrystallized from acetone-diisopropyl-ether

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

実験手順: To a suspension of 7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.6 g, 2.1 mmol) in tetrahydrofuran (10 ml) were added oxalyl chloride (0.33 ml, 4.3 mmol) and N,N-dimethylformamide (1 drop) at 0° C., and the mixture was stirred at room temperature for 2.5 hours. The solvent was evaporated, and the residue was dissolved in tetrahydrofuran (6 ml). To the mixture was dropwise added 4-(tert-butyldimethylsilyloxymethyl)aniline (0.56 g, 2.4 mmol) and triethylamine (0.36 ml, 2.6 mmol) in tetrahydrofuran. (2 ml) at 0° C., and the mixture was stirred at room temperature for 16 hours. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium chloride solution and dried with magnesium sulfate. The solvent was evaporated, and the residue was subjected to silica gel column chromatography. Crude amide (1.1 g) was obtained from fractions of hexane:ethyl acetate=5:1. This product was dissolved in acetone (8 ml), and to the mixture was dropwise added 6N hydrochloric acid. The mixture was stirred for 1 hour. To the mixture were added 1% sodium hydrogen carbonate (100 ml) and diisopropylether (100 ml), and precipitate was filtered, which were dissolved in acetone. The mixture was dried with magnesium sulfate, and the solvent was evaporated. The resulting powder was recrystallized from acetone-diisopropyl-ether to give N-(4-hydroxymethylphenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (0.87 g) as colorless crystals. The solvent was evaporated the residue was dissolved in tetrahydrofuran (6 ml) (2 ml) at 0° C., and the mixture was stirred at room temperature for 16 hours the mixture was extracted with ethyl acetate The extract was washed with saturated sodium chloride solution dried with magnesium sulfate The solvent was evaporated Crude amide (1.1 g) was obtained from fractions of hexane The mixture was stirred for 1 hour was filtered which were dissolved in acetone The mixture was dried with magnesium sulfate the solvent was evaporated The resulting powder was recrystallized from acetone-diisopropyl-ether

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

実験手順: In ethanol (80 ml) was dissolved tert-butyldimethyl-4-nitrobenzyloxysilane (16.5 g), and to the mixture was added dried 5% palladium on carbon (0.83 g). Under hydrogen atmosphere, the mixture was stirred at room temperature under atmospheric pressure for 7.5 hours. The palladium was filtered off, and the filtrate was concentrated. The residue was separated and purified with column chromatography (ethyl acetate/hexane=1/4) to give 4-aminobenzyloxy-tert-butyldimethylsilane (13.8 g) as colorless oil. to the mixture was added dried 5% palladium on carbon (0.83 g) The palladium was filtered off the filtrate was concentrated The residue was separated purified with column chromatography (ethyl acetate/hexane=1/4)

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

実験手順: In ethanol (80 ml) was dissolved tert-butyldimethyl-4-nitrobenzyloxysilane (16.5 g), and to the mixture was added dried 5% palladium on carbon (0.83 g). Under hydrogen atmosphere, the mixture was stirred at room temperature under atmospheric pressure for 7.5 hours. The palladium was filtered off, and the filtrate was concentrated. The residue was separated and purified with column chromatography (ethyl acetate/hexane=1/4) to give 4-aminobenzyloxy-tert-butyldimethylsilane (13.8 g) as colorless oil. to the mixture was added dried 5% palladium on carbon (0.83 g) The palladium was filtered off the filtrate was concentrated The residue was separated purified with column chromatography (ethyl acetate/hexane=1/4)

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

実験手順: To a suspension of 7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.6 g, 2.1 mmol) in tetrahydrofuran (10 ml) were added oxalyl chloride (0.33 ml, 4.3 mmol) and N,N-dimethylformamide (1 drop) at 0° C., and the mixture was stirred at room temperature for 2.5 hours. The solvent was evaporated, and the residue was dissolved in tetrahydrofuran (6 ml). To the mixture was dropwise added 4-(t-butyldimethylsilyloxymethyl)aniline (0.56 g, 2.4 mmol) and triethylamine (0.36 ml, 2.6 mmol) in tetrahydrofuran (2 ml) at 0° C., and the mixture was stirred at room temperature for 16 hours. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium chloride solution and dried with magnesium sulfate. The solvent was evaporated, and the residue was subjected to silica gel column chromatography. Crude amide (1.1 g) was obtained from fractions of hexane:ethyl acetate=5:1. This product was dissolved in acetone (8 ml), and to the mixture was dropwise added 6N hydrochloric acid. The mixture was stirred for 1 hour. To the mixture were added 1% sodium hydrogen carbonate (100 ml) and diisopropylether (100 ml), and precipitate was filtered, which were dissolved in acetone. The mixture was dried with magnesium sulfate, and the solvent was evaporated. The resulting powder was recrystallized from acetone-diisopropyl-ether to give N-(4-hydroxymethylphenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (0.87 g) as colorless crystals. The solvent was evaporated the residue was dissolved in tetrahydrofuran (6 ml) at 0° C. the mixture was stirred at room temperature for 16 hours the mixture was extracted with ethyl acetate The extract was washed with saturated sodium chloride solution dried with magnesium sulfate The solvent was evaporated Crude amide (1.1 g) was obtained from fractions of hexane The mixture was stirred for 1 hour was filtered which were dissolved in acetone The mixture was dried with magnesium sulfate the solvent was evaporated The resulting powder was recrystallized from acetone-diisopropyl-ether

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4-(((tert-butyldimethylsilyl)oxy)methyl)aniline (14.0 g, 59 mmol) in a mixture of anhydrous DMF (30 mL) and anhydrous dioxane (30 mL) in a 250 mL 3-necked round-bottomed flask equipped with a constant addition funnel (60 mL) was cooled to 0° C. using an ice-bath. Bromoacetyl bromide (11.91 g, 5.18 mL, 59 mmol) was added dropwise, keeping the internal temperature between 0° and 5° C. over a 1/2 h period. After the addition of the bromoacetyl bromide was completed, the solution was warmed to rt, stirred overnight, and then the solution was slowly poured into 500 mL of ice-water. The resulting precipitate was filtered, washed with water, and then dried in a vacuum dessicator overnight to afford 8.73 g (61%) Of the title compound as a pale yellow crystals, mp 128°-134° C. (decomp), became wet at 89°-93° C.: 1H NMR (DMSO-d6) δ10.35 (s, 1H), 7.52 (d, J=8.8, 2H), 7.26 (d, J=8.8, 2H), 4.43 (s, 2H), 4.04 (s, 2H); 13C NMR (DMSO-d6) δ164.58, 138.00, 137.15, 126.97, 118.94, 62.51, 30.43; MS (El, m/z) 243 (M+). equipped with a constant addition funnel (60 mL) the internal temperature between 0° and 5° C. over a 1/2 h the solution was warmed to rt The resulting precipitate was filtered washed with water dried in a vacuum dessicator overnight