methyl 2-amino-3-oxo-3-phenylpropanoate

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: (2R)-2-tert-Butoxycarbonylamino-3-(2-naphthyl)propionic acid (5.49 g; 17.42 mmol) was dissolved in dry tetrahydrofuran (200 ml) and N-methylmorpholine (1.92 ml; 17.42 mmol) was added. The reaction mixture was cooled to -20° C. and stirred 15 min. Isobutyl chloroformate (2.27 ml; 17.42 mmol) was dissolved in dry tetrahydrofuran (3 ml) and added dropwise to the reaction mixture at -20° C. N-methylmorpholine (1.92 ml; 17.42 mmol) and 2-amino-3-oxo-3-phenylpropionic acid methylester (4.0 g; 17.42 mmol) were added and and the mixture was stirred 30 min at -20° C. The reaction mixture was heated to room temperature and the solvent was removed in vacuo. The residue was dissolved in methylene chloride (200 ml), washed with water (200 ml) and dried (magnesium sulfate). The solvent was removed in vacuo and the residue was chromatographed on silica (5×45 cm) using heptane/ethyl acetate/methylene chloride (2:1:1) as eluent to afford 6.19 g of a diastereomeric mixture of 2-((2R)-2-tert-butoxycarbonylamino-3-(2-naphthyl)propionylamino)-3-oxo-3-phenylpropionic acid methylester. added dropwise to the reaction mixture at -20° C the mixture was stirred 30 min at -20° C The reaction mixture was heated to room temperature the solvent was removed in vacuo The residue was dissolved in methylene chloride (200 ml) washed with water (200 ml) dried (magnesium sulfate) The solvent was removed in vacuo the residue was chromatographed on silica (5×45 cm)

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

実験手順: (2R)-2-tert-Butoxycarbonylamino-3-(2-naphthyl)propionic acid (5.49 g; 17.42 mmol) was dissolved in dry tetrahydrofuran (200 ml) and N-methylmorpholine (1.92 ml; 17.42 mmol) was added. The reaction mixture was cooled to -20° C. and stirred 15 min. Isobutyl chloroformate (2.27 ml; 17.42 mmol) was dissolved in dry tetrahydrofuran (3 ml) and added dropwise to the reaction mixture at -20° C. N-methylmorpholine (1.92 ml; 17.42 mmol) and 2-amino-3-oxo-3-phenylpropionic acid methylester (4.0 g; 17.42 mmol) were added and and the mixture was stirred 30 min at -20° C. The reaction mixture was heated to room temperature and the solvent was removed in vacuo. The residue was dissolved in methylene chloride (200 ml), washed with water (200 ml) and dried (magnesium sulfate). The solvent was removed in vacuo and the residue was chromatographed on silica (5×45 cm) using heptane/ethyl acetate/methylene chloride (2:1:1) as eluent to afford 6.19 g of a diastereomeric mixture of 2-((2R)-2-tert-butoxycarbonylamino-3-(2-naphthyl)propionylamino)-3-oxo-3-phenylpropionic acid methylester. added dropwise to the reaction mixture at -20° C the mixture was stirred 30 min at -20° C The reaction mixture was heated to room temperature the solvent was removed in vacuo The residue was dissolved in methylene chloride (200 ml) washed with water (200 ml) dried (magnesium sulfate) The solvent was removed in vacuo the residue was chromatographed on silica (5×45 cm)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dry tetrahydrofuran (250 ml) was cooled to -78° C. Potassium tert-butoxide (6.37 g; 56.72 mmol) was dissolved in dry tetrahydrofuran (100 ml) and added. (Benzhydrylideneamino)acetic acid methyl ester (14.35 g; 56.72 mmol) was added and the reaction mixture was stirred 30 min at -78° C. Benzoyl chloride (6.59 g; 56.72 mmol) was added dropwise and the reaction mixture was stirred 30 min at -78° C. Hydrochloric acid (1.0 M; 175 ml) was added dropwise. The reaction mixture was heated to room temperature and 2/3 of the solvent was removed in vacuo. Water (700 ml) was added and the reaction mixture was washed with diethyl ether (400 ml). The aqueous phase was evaporated in vacuo and the residue was dissolved in methanol and evaporated (2×150 ml). Methanol (80 ml) was added. The mixture was filtrated and the filtrate was evaporated in vacuo. The residue was recrystallised from tetrahydrofuran/diethyl ether to afford 8.86 g of 2-amino-3-oxo-3-phenylpropionic acid methylester as a hydrochloride. added the reaction mixture was stirred 30 min at -78° C The reaction mixture was heated to room temperature 2/3 of the solvent was removed in vacuo Water (700 ml) was added the reaction mixture was washed with diethyl ether (400 ml) The aqueous phase was evaporated in vacuo the residue was dissolved in methanol evaporated (2×150 ml) Methanol (80 ml) was added The mixture was filtrated the filtrate was evaporated in vacuo The residue was recrystallised from tetrahydrofuran/diethyl ether

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

実験手順: (2R)-2-tert-Butoxycarbonylamino-3-(2-naphthyl)propionic acid (5.49 g; 17.42 mmol) was dissolved in dry tetrahydrofuran (200 ml) and N-methylmorpholine (1.92 ml; 17.42 mmol) was added. The reaction mixture was cooled to −20° C. and stirred 15 min. Isobutyl chloroformate (2.27 ml; 17.42 mmol) was dissolved in dry tetrahydrofuran (3 ml) and added dropwise to the reaction mixture at −20° C. N-methylmorpholine (1.92 ml; 17.42 mmol) and 2-amino-3-oxo-3-phenylpropionic acid methylester (4.0 g; 17.42 mmol) were added and and the mixture was stirred 30 min at −20° C. The reaction mixture was heated to room temperature and the solvent was. removed in vacuo. The residue was dissolved in methylene chloride (200 ml), washed with water (200 ml) and dried (magnesium sulfate). The solvent was removed in vacuo and the residue was chromatographed on silica (5×45 cm) using heptane/ethyl acetate/methylene chloride (2:1:1) as eluent to afford 6.19 g of a diastereomeric mixture of 2-((2R)-2-tert-butoxycarbonylamino-3-(2-naphthyl)propionylamino)-3-oxo-3-phenylpropionic acid methylester. added dropwise to the reaction mixture at −20° C the mixture was stirred 30 min at −20° C The reaction mixture was heated to room temperature removed in vacuo The residue was dissolved in methylene chloride (200 ml) washed with water (200 ml) dried (magnesium sulfate) The solvent was removed in vacuo the residue was chromatographed on silica (5×45 cm)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dry tetrahydrofuran (250 ml) was cooled to −78° C. Potassium tert-butoxide (6.37 g; 56.72 mmol) was dissolved in dry tetrahydrofuran (100 ml) and added. (Benzhydrylideneamino) acetic acid methyl ester (14.35 g; 56.72 mmol) was added and the reaction mixture was stirred 30 min at −78° C. Benzoyl chloride (6.59 g; 56.72 mmol) was added dropwise and the reaction mixture was stirred 30 min at −78° C. Hydrochloric acid (1.0 M; 175 ml) was added dropwise. The reaction mixture was heated to room temperature and 2/3 of the solvent was removed in vacuo. Water (700 ml) was added and the reaction mixture was washed with diethyl ether (400 ml). The aqueous phase was evaporated in vacuo and the residue was dissolved in methanol and evaporated (2×150 ml). Methanol (80 ml) was added. The mixture was filtrated and the filtrate was evaporated in vacuo. The residue was recrystallised from tetrahydrofuran/diethyl ether to afford 8.86 g of 2-amino-3-oxo-3-phenylpropionic acid methylester as a hydrochloride. added the reaction mixture was stirred 30 min at −78° C The reaction mixture was heated to room temperature 2/3 of the solvent was removed in vacuo Water (700 ml) was added the reaction mixture was washed with diethyl ether (400 ml) The aqueous phase was evaporated in vacuo the residue was dissolved in methanol evaporated (2×150 ml) Methanol (80 ml) was added The mixture was filtrated the filtrate was evaporated in vacuo The residue was recrystallised from tetrahydrofuran/diethyl ether

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

実験手順: (2R)-2-tert-Butoxycarbonylamino-3-(2-naphthyl)propionic acid (5.49 g; 17.42 mmol) was dissolved in dry tetrahydrofuran (200 ml) and N-methylmorpholine (1.92 ml; 17.42 mmol) was added. The reaction mixture was cooled to -20° C. and stirred 15 min. Isobutyl chloroformate (2.27 ml; 17.42 mmol) was dissolved in dry tetrahydrofuran (3 ml) and added dropwise to the reaction mixture at -20° C. N-methylmorpholine (1.92 ml; 17.42 mmol) and 2-amino-3-oxo-3-phenylpropionic acid methylester (4.0 g; 17.42 mmol) were added and and the mixture was stirred 30 min at -20° C. The reaction mixture was heated to room temperature and the solvent was removed in vacuo. The residue was dissolved in methylene chloride (200 ml), washed with water (200 ml) and dried (magnesium sulfate). The solvent was removed in vacuo and the residue was chromatographed on silica (5×45 cm) using heptane/ethyl acetate/methylene chloride (2:1:1) as eluent to afford 6.19 g of a diastereomeric mixture of 2-((2R)-2-tert-butoxycarbonylamino-3-(2-naphthyl)propionylamino)-3-oxo-3-phenylpropionic acid methylester. added dropwise to the reaction mixture at -20° C the mixture was stirred 30 min at -20° C The reaction mixture was heated to room temperature the solvent was removed in vacuo The residue was dissolved in methylene chloride (200 ml) washed with water (200 ml) dried (magnesium sulfate) The solvent was removed in vacuo the residue was chromatographed on silica (5×45 cm)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dry tetrahydrofuran (250 ml) was cooled to -78° C. Potassium tert-butoxide (6.37 g; 56.72 mmol) was dissolved in dry tetrahydrofuran (100 ml) and added. (Benzhydrylideneamino)acetic acid methyl ester (14.35 g; 56.72 mmol) was added and the reaction mixture was stirred 30 min at -78° C. Benzoyl chloride (6.59 g; 56.72 mmol) was added dropwise and the reaction mixture was stirred 30 min at -78° C. Hydrochloric acid (1.0 M; 175 ml) was added dropwise. The reaction mixture was heated to room temperature and 2/3 of the solvent was removed in vacuo. Water (700 ml) was added and the reaction mixture was washed with diethyl ether (400 ml). The aqueous phase was evaporated in vacuo and the residue was dissolved in methanol and evaporated (2×150 ml). Methanol (80 ml) was added. The mixture was filtrated and the filtrate was evaporated in vacuo. The residue was recrystallised from tetrahydrofuran/diethyl ether to afford 8.86 g of 2-amino-3-oxo-3-phenylpropionic acid methylester as a hydrochloride. added the reaction mixture was stirred 30 min at -78° C The reaction mixture was heated to room temperature 2/3 of the solvent was removed in vacuo Water (700 ml) was added the reaction mixture was washed with diethyl ether (400 ml) The aqueous phase was evaporated in vacuo the residue was dissolved in methanol evaporated (2×150 ml) Methanol (80 ml) was added The mixture was filtrated the filtrate was evaporated in vacuo The residue was recrystallised from tetrahydrofuran/diethyl ether