[chloro(methyl)phosphoryl]benzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Methylphenyl-phosphinic chloride (1.05 g, 6 mmol) is dissolved in dichloromethane (50 mL) and cooled to 0° C. To this is added a solution of N-hexyl-D-alanine methyl ester (1 g, 5.34 mmol) and triethylamine (2.1 mL, 15 mmol) in dichloromethane (10 mL). A catalytic amount of 4-dimethylaminopyridine is added and reaction is stirred for 16 hours, washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified by silica gel flash chromatography (100% ethyl acetate) to give N-((R)-methylphenylphosphinyl)-N-hexyl-D-alanine methyl ester as an oil. reaction washed with water and brine dried over sodium sulfate concentrated The crude product is purified by silica gel flash chromatography (100% ethyl acetate)

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

実験手順: Methylphenylphosphinic chloride (12.23 g, 70 mmol) is taken up in dichloromethane (100 mL) and cooled to 0° C. To this is added a solution of N-(3-picolyl) D-leucine methyl ester (15.5 g, 65.6 mmol) and N-methyl morpholine (19.24 mL, 175 mmol) in dichloromethane (100 mL). A catalytic amount of 4-dimethylaminopyridine is added and the reaction stirs for 16 hours at room temperature. More methylphenylphosphinic chloride is added (2 g, 11.46 mmol). The reaction continues to stir for 24 hours until complete. By TLC, the diastereomers do not separate. The product is purified by silica gel flash chromatography (5:95 ethanol:ethyl acetate) to give N-((R/S)-methylphenyl-phosphinyl)-N-(3-picolyl) D-leucine methyl ester as an oil. To this ester is added a solution of NH2OK (250 mL, 1.76M in methanol) prepared as described in Fieser and Fieser, Vol. 1, p. 478. The reaction is stirred for 16 hours at which time TLC indicates completion. The reaction mixture is neutralized with 1M aqueous HCl and the volatiles are removed. The product is purified by silica gel flash chromatography (10:90 ethanol:ethyl acetate) to give 8.6 g of N-hydroxy-2(R)-[[(R/S)-methylphenylphosphinyl]3-picolylamino]-4-methylpentanamide as a 60 (R)/40 (S) mixture of diastereomers: MS-IS m/z 376 [M+H]+, 398[M+Na]+. (R1 =3-pyridyl methyl, R2 =isobutyl, R3 =methyl, R4 =phenyl). By TLC, the diastereomers do not separate The product is purified by silica gel flash chromatography (5:95 ethanol:ethyl acetate)

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

実験手順: Methylphenyl-phosphinic chloride (361 mg, 2.07 mmol) is dissolved in dichloromethane (2.5 mL) and then cooled to 0° C. To this is added a solution of N-benzyl D-alanine methyl ester (400 mg, 2.07 mmol) and N-methyl morpholine (0.51 mL, 4.6 mmol) in dichloromethane (2.5 mL). A catalytic amount of 4-dimethylaminopyridine is then added to the stirring mixture. The reaction is stirred for 16 hours at room temperature, washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified by silica gel flash chromatography (100% ethyl acetate) to give N-((R)-methylphenylphosphinyl)-N-benzyl-D-leucine methyl ester as an oil. washed with water and brine dried over sodium sulfate concentrated The crude product is purified by silica gel flash chromatography (100% ethyl acetate)

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

実験手順: Methylphenyl-phosphinic chloride (1.05 g, 6 mmol) is dissolved in dichloromethane (50 mL) and cooled to 0° C. To this is added a solution of N-hexyl-D-alanine methyl ester (1 g, 5.34 mmol) and triethylamine (2.1 mL, 15 mmol) in dichloromethane (10 mL). A catalytic amount of 4-dimethylaminopyridine is added and reaction is stirred for 16 hours, washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified by silica gel flash chromatography (100% ethyl acetate) to give N-((R)-methylphenylphosphinyl)-N-hexyl-D-alanine methyl ester as an oil. reaction washed with water and brine dried over sodium sulfate concentrated The crude product is purified by silica gel flash chromatography (100% ethyl acetate)

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

実験手順: Methylphenylphosphinic chloride (12.23 g, 70 mmol) is taken up in dichloromethane (100 mL) and cooled to 0° C. To this is added a solution of N-(3-picolyl) D-leucine methyl ester (15.5 g, 65.6 mmol) and N-methyl morpholine (19.24 mL, 175 mmol) in dichloromethane (100 mL). A catalytic amount of 4-dimethylaminopyridine is added and the reaction stirs for 16 hours at room temperature. More methylphenylphosphinic chloride is added (2 g, 11.46 mmol). The reaction continues to stir for 24 hours until complete. By TLC, the diastereomers do not separate. The product is purified by silica gel flash chromatography (5:95 ethanol:ethyl acetate) to give N-((R/S)-methylphenyl-phosphinyl)-N-(3-picolyl) D-leucine methyl ester as an oil. To this ester is added a solution of NH2OK (250 mL, 1.76M in methanol) prepared as described in Fieser and Fieser, Vol. 1, p. 478. The reaction is stirred for 16 hours at which time TLC indicates completion. The reaction mixture is neutralized with 1M aqueous HCl and the volatiles are removed. The product is purified by silica gel flash chromatography (10:90 ethanol:ethyl acetate) to give 8.6 g of N-hydroxy-2(R)-[[(R/S)-methylphenylphosphinyl]3-picolylamino]-4-methylpentanamide as a 60 (R)/40 (S) mixture of diastereomers: MS-IS m/z 376 [M+H]+, 398[M+Na]+. (R1 =3-pyridyl methyl, R2 =isobutyl, R3 =methyl, R4 =phenyl). By TLC, the diastereomers do not separate The product is purified by silica gel flash chromatography (5:95 ethanol:ethyl acetate)

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

実験手順: Methylphenylphosphinic chloride (12.23 g, 70 mmol) is taken up in dichloromethane (100 mL) and cooled to 0° C. To this is added a solution of N-(3-picolyl) D-leucine methyl ester (15.5 g, 65.6 mmol) and N-methyl morpholine (19.24 mL, 175 mmol) in dichloromethane (100 mL). A catalytic amount of 4-dimethylaminopyridine is added and the reaction stirs for 16 hours at room temperature. More methylphenylphosphinic chloride is added (2 g, 11.46 mmol). The reaction continues to stir for 24 hours until complete. By TLC, the diastereomers do not separate. The product is purified by silica gel flash chromatography (5:95 ethanol:ethyl acetate) to give N-((R/S)-methylphenyl-phosphinyl)-N-(3-picolyl) D-leucine methyl ester as an oil. To this ester is added a solution of NH2OK (250 mL, 1.76M in methanol) prepared as described in Fieser and Fieser, Vol. 1, p. 478. The reaction is stirred for 16 hours at which time TLC indicates completion. The reaction mixture is neutralized with 1M aqueous HCl and the volatiles are removed. The product is purified by silica gel flash chromatography (10:90 ethanol:ethyl acetate) to give 8.6 g of N-hydroxy-2(R)-[[(R/S)-methylphenylphosphinyl]3-picolylamino]-4-methylpentanamide as a 60 (R)/40 (S) mixture of diastereomers: MS-IS m/z 376 [M+H]+, 398[M+Na]+. (R1 =3-pyridyl methyl, R2 =isobutyl, R3 =methyl, R4 =phenyl). By TLC, the diastereomers do not separate The product is purified by silica gel flash chromatography (5:95 ethanol:ethyl acetate)

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

実験手順: Methylphenyl-phosphinic chloride (361 mg, 2.07 mmol) is dissolved in dichloromethane (2.5 mL) and then cooled to 0° C. To this is added a solution of N-benzyl D-alanine methyl ester (400 mg, 2.07 mmol) and N-methyl morpholine (0.51 mL, 4.6 mmol) in dichloromethane (2.5 mL). A catalytic amount of 4-dimethylaminopyridine is then added to the stirring mixture. The reaction is stirred for 16 hours at room temperature, washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified by silica gel flash chromatography (100% ethyl acetate) to give N-((R)-methylphenylphosphinyl)-N-benzyl-D-leucine methyl ester as an oil. washed with water and brine dried over sodium sulfate concentrated The crude product is purified by silica gel flash chromatography (100% ethyl acetate)

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

実験手順: Methylphenyl-phosphinic chloride (361 mg, 2.07 mmol) is dissolved in dichloromethane (2.5 mL) and then cooled to 0° C. To this is added a solution of N-benzyl D-alanine methyl ester (400 mg, 2.07 mmol) and N-methyl morpholine (0.51 mL, 4.6 mmol) in dichloromethane (2.5 mL). A catalytic amount of 4-dimethylaminopyridine is then added to the stirring mixture. The reaction is stirred for 16 hours at room temperature, washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified by silica gel flash chromatography (100% ethyl acetate) to give N-((R)-methylphenylphosphinyl)-N-benzyl-D-leucine methyl ester as an oil. washed with water and brine dried over sodium sulfate concentrated The crude product is purified by silica gel flash chromatography (100% ethyl acetate)

反応条件: temp:0.00; pressure:0.00; stir: