methyl 3-(4-chlorophenyl)-2-formamidopropanoate

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

実験手順: (±)-(4-Chlorophenyl)alanine methyl ester hydrochloride (2.00 g) was suspended in methylene chloride (20 ml), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.60 g), 1-hydroxybenzotriazole monohydrate (1.23 g), N-methylmorpholine (1.90 ml) and formic acid (0.30 ml) were added to stir the mixture for 15 minutes. After a process in which formic acid (0.30 ml) was additionally added to stir the mixture for 15 minutes was repeated 3 times, the reaction mixture was diluted with methylene chloride. After an ogranic layer was washed with water and then dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (methylene chloride:methanol=40:1) to obtain the title compound (1.21 g). to stir the mixture for 15 minutes After an ogranic layer was washed with water dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue was purified by column chromatography on silica gel (methylene chloride:methanol=40:1)

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

実験手順: (±)-(4-Chlorophenyl)alanine methyl ester hydrochloride (2.00 g) was suspended in methylene chloride (20 ml), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.60 g), 1-hydroxybenzotriazole monohydrate (1.23 g), N-methylmorpholine (1.90 ml) and formic acid (0.30 ml) were added to stir the mixture for 15 minutes. After a process in which formic acid (0.30 ml) was additionally added to stir the mixture for 15 minutes was repeated 3 times, the reaction mixture was diluted with methylene chloride. After an ogranic layer was washed with water and then dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (methylene chloride:methanol=40:1) to obtain the title compound (1.21 g). to stir the mixture for 15 minutes After an ogranic layer was washed with water dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue was purified by column chromatography on silica gel (methylene chloride:methanol=40:1)

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

実験手順: (±)-(4-Chlorophenyl)alanine methyl ester hydrochloride (2.00 g) was suspended in methylene chloride (20 mL), and to the suspension were added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.60 g), 1-hydroxybenzotriazole monohydrate (1.23 g), N-methylmorpholine (1.90 mL), and formic acid (0.30 mL), followed by stirring for 15 minutes. Subsequently, formic acid (0.30 mL) addition and subsequent stirring for 15 minutes were repeated 3 times. The reaction mixture was diluted with methylene chloride. The organic layer was washed with water, and was dried over sodium sulfate anhydrate. The solvent was distilled away under reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride:methanol=40:1), to thereby give the title compound (1.21 g). subsequent stirring for 15 minutes The organic layer was washed with water was dried over sodium sulfate anhydrate The solvent was distilled away under reduced pressure the residue was purified by silica gel column chromatography (methylene chloride:methanol=40:1)

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

実験手順: (±)-(4-Chlorophenyl)alanine methyl ester hydrochloride (2.00 g) was suspended in methylene chloride (20 ml), and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (1.60 g), 1-hydroxybenzo-triazole monohydrate (1.23 g), N-methylmorpholine (1.90 ml) and formic acid (0.30 ml) were added to stir the mixture for 15 minutes. After a process in which formic acid (0.30 ml) was additionally added to stir the mixture for 15 minutes was repeated 3 times, the reaction mixture was diluted with methylene chloride. After an ogranic layer was washed with water and then dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (methylene chloride:methanol=40:1) to obtain the title compound (1.21 g). to stir the mixture for 15 minutes After an ogranic layer was washed with water dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue was purified by column chromatography on silica gel (methylene chloride:methanol=40:1)

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

実験手順: Oxalyl choride (5.7 mL) was added dropwise to a solution of 3-(4-chlorophenyl)-2-formylamino-propanoic acid methyl ester (14.5 g, 60 mmol) in CH2Cl2 (400 mL) at room temperature. After stirring for 0.5 hour, ferric chloride (11.7 g) was added and the mixture was stirred for 48 hours. The reaction mixture was diluted with water (500 mL). The organic layer was separated, and the aqueous layer was re-extracted with CH2Cl2 (2×300 mL). The organic layers were combined, washed with brine (200 mL), dried over anhydrous Na2SO4, filtered and concentrated to dryness. The residue was dissolved in MeOH (400 mL), sulfuric acid (20 mL, 98%) was added and the mixture was heated under reflux for 48 hours. After cooled to room temperature, the reaction mixture was diluted with 5% sodium bicarbonate solution (1 L). The organic layer was separated, and the aqueous layer was re-extracted with CH2Cl2 (2×500 mL). The organic layers were combined, washed with brine (500 mL), dried over anhydrous Na2SO4, filtered and concentrated to dryness. The crude material was further purified by silica gel chromatography (EtOAc/Hexane=1/3) and afforded the title compound (3.1 g, 23.3% yield) as a yellow solid. 1H NMR (300 MHz, CDCl3): 9.26 (s, 1H), 8.51 (s, 1H), 8.05 (d, J=1.8 Hz, 1H), 7.93 (d, J=8.7 Hz, 1H), 7.73 (dd, J=1.8 and 8.7 Hz, 1H), 4.06 (s, 3H). the mixture was stirred for 48 hours The organic layer was separated the aqueous layer was re-extracted with CH2Cl2 (2×300 mL) washed with brine (200 mL) dried over anhydrous Na2SO4 filtered concentrated to dryness The residue was dissolved in MeOH (400 mL) sulfuric acid (20 mL, 98%) was added the mixture was heated under reflux for 48 hours the reaction mixture was diluted with 5% sodium bicarbonate solution (1 L) The organic layer was separated the aqueous layer was re-extracted with CH2Cl2 (2×500 mL) washed with brine (500 mL) dried over anhydrous Na2SO4 filtered concentrated to dryness The crude material was further purified by silica gel chromatography (EtOAc/Hexane=1/3)

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

実験手順: (±)-(4-Chlorophenyl)alanine methyl ester hydrochloride (2.00 g) was suspended in methylene chloride (20 ml), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.60 g), 1-hydroxybenzotriazole monohydrate (1.23 g), N-methylmorpholine (1.90 ml) and formic acid (0.30 ml) were added to stir the mixture for 15 minutes. After a process in which formic acid (0.30 ml) was additionally added to stir the mixture for 15 minutes was repeated 3 times, the reaction mixture was diluted with methylene chloride. After an ogranic layer was washed with water and then dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (methylene chloride:methanol=40:1) to obtain the title compound (1.21 g). to stir the mixture for 15 minutes After an ogranic layer was washed with water dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue was purified by column chromatography on silica gel (methylene chloride:methanol=40:1)