tert-butyl N-[2-oxo-2-(phenylmethoxyamino)ethyl]carbamate

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

実験手順: T-Butyloxycarbonyl-O-benzyl glycine hydroxamic acid [(17.5 g, 62.5 mMol) see Step A] was dissolved in trifluoroacetic acid (25 ml), stirred at room temperature thirty minutes, and ether (200 ml) added. The product was filtered and dried to yield: 9.0 g, m.p. 122°-124°. The product was filtered dried to yield: 9.0 g, m.p. 122°-124°

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

実験手順: T-Butyloxycarbonyl-O-benzyl glycine hydroxamic acid [(17.5 g, 62.5 mMol) see Step A] was dissolved in trifluoroacetic acid (25 ml), stirred at room temperature thirty minutes, and ether (200 ml) added. The product was filtered and dried to yield: 9.0 g, m.p. 122°-124°. The product was filtered dried to yield: 9.0 g, m.p. 122°-124°

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

実験手順: O-Benzylhydroxylamine hydrochloride (15.0 g, 93.8 mMol) was dissolved in methanol (150 ml) and added to a solution of potassium hydroxide (5.27 g, 93.8 mMol) in methanol (50 ml). The resulting mixture was cooled, filtered, evaporated, dissolved in tetrahydrofuran (25 ml) and filtered as solution A. t-Butyloxycarbonyl glycine (16.4 g, 93.8 mMol) was dissolved in tetrahydrofuran (75 ml), triethylamine (13.2 ml, 93.8 mMol) added and the solution cooled to -10° C. with dry ice/ethanol. Iso-butyl chloroformate (12.2 ml, 93.8 mMol) was added and the solution stirred cold 2 minutes, before adding solution A dropwise. The mixture was stirred cold 1 hour and at room temperature 2 hours, filtered, evaporated, dissolved in ethyl acetate (100 ml), washed with water (3× 50 ml), dried over magnesium sulfate and evaporated to an oil. The resulting mixture was cooled filtered evaporated dissolved in tetrahydrofuran (25 ml) filtered as solution A The mixture was stirred cold 1 hour and at room temperature 2 hours filtered evaporated dissolved in ethyl acetate (100 ml) washed with water (3× 50 ml) dried over magnesium sulfate evaporated to an oil

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: HCl·NH2OBzl (11.2 g; 70.2 mmol) was suspended in DMF (100 ml) and TEA (11.2 ml; 80.0 mmol) was added dropwise under ice-cooling. HOBt (7.43 g; 55.0 mmol) and Boc-Gly-OH (8.76 g; 50.0 mmol) were then added and the mixture was cooled with a coolant at -20° C. DCC (14.5 g; 70.2 mmol) dissolved in CH2Cl2 (70 ml) was added dropwise. After the dropwise addition, the reaction was allowed to proceed for 1 hour at -10° C. and overnight in a refrigerator. Insolubles were filtered off and the solvent was distilled off under reduced pressure. The residue was dissolved in AcOEt and then washed successively with water, 1N-HCl, water, 10% Na2CO3 and water. The solution was dried over anhydrous MgSO4 and the solvent was distilled off under reduced pressure. The residue was purified by chromatography on silica gel (Fuji Davison BW 200, 300 g; eluted with AcOEt: n-Hexane (=1:1) mixed solvent) to give Boc-Gly-NHOBzl (13 g; 93%) as a pale yellow oil. cooling was added dropwise After the dropwise addition Insolubles were filtered off the solvent was distilled off under reduced pressure The residue was dissolved in AcOEt washed successively with water, 1N-HCl, water, 10% Na2CO3 and water The solution was dried over anhydrous MgSO4 the solvent was distilled off under reduced pressure The residue was purified by chromatography on silica gel (Fuji Davison BW 200, 300 g; eluted with AcOEt: n-Hexane (=1:1) mixed solvent)

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: HCl·NH2OBzl (11.2 g; 70.2 mmol) was suspended in DMF (100 ml) and TEA (11.2 ml; 80.0 mmol) was added dropwise under ice-cooling. HOBt (7.43 g; 55.0 mmol) and Boc-Gly-OH (8.76 g; 50.0 mmol) were then added and the mixture was cooled with a coolant at -20° C. DCC (14.5 g; 70.2 mmol) dissolved in CH2Cl2 (70 ml) was added dropwise. After the dropwise addition, the reaction was allowed to proceed for 1 hour at -10° C. and overnight in a refrigerator. Insolubles were filtered off and the solvent was distilled off under reduced pressure. The residue was dissolved in AcOEt and then washed successively with water, 1N-HCl, water, 10% Na2CO3 and water. The solution was dried over anhydrous MgSO4 and the solvent was distilled off under reduced pressure. The residue was purified by chromatography on silica gel (Fuji Davison BW 200, 300 g; eluted with AcOEt: n-Hexane (=1:1) mixed solvent) to give Boc-Gly-NHOBzl (13 g; 93%) as a pale yellow oil. cooling was added dropwise After the dropwise addition Insolubles were filtered off the solvent was distilled off under reduced pressure The residue was dissolved in AcOEt washed successively with water, 1N-HCl, water, 10% Na2CO3 and water The solution was dried over anhydrous MgSO4 the solvent was distilled off under reduced pressure The residue was purified by chromatography on silica gel (Fuji Davison BW 200, 300 g; eluted with AcOEt: n-Hexane (=1:1) mixed solvent)

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

実験手順: T-Butyloxycarbonyl-O-benzyl glycine hydroxamic acid [(17.5 g, 62.5 mMol) see Step A] was dissolved in trifluoroacetic acid (25 ml), stirred at room temperature thirty minutes, and ether (200 ml) added. The product was filtered and dried to yield: 9.0 g, m.p. 122°-124°. The product was filtered dried to yield: 9.0 g, m.p. 122°-124°

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

実験手順: O-Benzylhydroxylamine hydrochloride (15.0 g, 93.8 mMol) was dissolved in methanol (150 ml) and added to a solution of potassium hydroxide (5.27 g, 93.8 mMol) in methanol (50 ml). The resulting mixture was cooled, filtered, evaporated, dissolved in tetrahydrofuran (25 ml) and filtered as solution A. t-Butyloxycarbonyl glycine (16.4 g, 93.8 mMol) was dissolved in tetrahydrofuran (75 ml), triethylamine (13.2 ml, 93.8 mMol) added and the solution cooled to -10° C. with dry ice/ethanol. Iso-butyl chloroformate (12.2 ml, 93.8 mMol) was added and the solution stirred cold 2 minutes, before adding solution A dropwise. The mixture was stirred cold 1 hour and at room temperature 2 hours, filtered, evaporated, dissolved in ethyl acetate (100 ml), washed with water (3× 50 ml), dried over magnesium sulfate and evaporated to an oil. The resulting mixture was cooled filtered evaporated dissolved in tetrahydrofuran (25 ml) filtered as solution A The mixture was stirred cold 1 hour and at room temperature 2 hours filtered evaporated dissolved in ethyl acetate (100 ml) washed with water (3× 50 ml) dried over magnesium sulfate evaporated to an oil