2-(2,6-dimethylphenoxy)acetyl chloride

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:; See reaction.notes.procedure_details.

実験手順: Oxallyl chloride (36.3 ml, 0.42 mol) was added to a slurry of 2-6 dimethylphenoxyacetic acid (50 g, 0.28 mol) in 500 ml toluene followed by addition of 5 drops of DMF and stirred at room temperature for 30 min, then at 55° C. for 1.5 hours. The toluene was removed on a rotary evaporator and remaining volatiles were removed in vacuo to afford 2,6-dimethyl-phenoxyacetyl chloride as an amber oil, 55 grams, 100%. [2S,3S,5S]-2-Amino-3-hydroxy-5-t-butyloxycarbonylamino-1,6-diphenylhexane×0.5 succinate (111.9 g, 0.25 mol) was charged to a 2 L, 3-necked round-bottomed flask with mechanical stirring. NaHCO3 (106 9, 1.26 mol), 600 ml H2O and 600 ml EtOAc were added and stirred vigorously until all solids were dissolved (15 minutes). Stirring was slowed and a solution of the 2,6-dimethyl-phenoxyacetyl chloride and EtOAc (100 ml) was added in a narrow stream via addition funnel. After 30 min of stirring, starting materials were consumed (HPLC analysis) and the layers were separated. The aqueous layer was extracted with EtOAc, the organic layers were combined and washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine, dried over MgSO4, filtered and concentrated to provide the desired product as a white solid. were dissolved (15 minutes) Stirring After 30 min of stirring were consumed (HPLC analysis) the layers were separated The aqueous layer was extracted with EtOAc washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine dried over MgSO4 filtered concentrated

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

実験手順: Oxallyl chloride (36.3 ml, 0.42 mol) was added to a slurry of 2-6 dimethylphenoxyacetic acid (50 g, 0.28 mol) in 500 ml toluene followed by addition of 5 drops of DMF and stirred at room temperature for 30 min, then at 55° C. for 1.5 hours. The toluene was removed on a rotary evaporator and remaining volatiles were removed in vacuo to afford 2,6-dimethyl-phenoxyacetyl chloride as an amber oil, 55 grams, 100%. [2S,3S,5S]-2-Amino-3-hydroxy-5-t-butyloxycarbonylamino-1,6-diphenylhexane×0.5 succinate (111.9 g, 0.25 mol) was charged to a 2 L, 3-necked round-bottomed flask with mechanical stirring. NaHCO3 (106 9, 1.26 mol), 600 ml H2O and 600 ml EtOAc were added and stirred vigorously until all solids were dissolved (15 minutes). Stirring was slowed and a solution of the 2,6-dimethyl-phenoxyacetyl chloride and EtOAc (100 ml) was added in a narrow stream via addition funnel. After 30 min of stirring, starting materials were consumed (HPLC analysis) and the layers were separated. The aqueous layer was extracted with EtOAc, the organic layers were combined and washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine, dried over MgSO4, filtered and concentrated to provide the desired product as a white solid. were dissolved (15 minutes) Stirring After 30 min of stirring were consumed (HPLC analysis) the layers were separated The aqueous layer was extracted with EtOAc washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine dried over MgSO4 filtered concentrated

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

実験手順: [2S,3S,5S]-2-Amino-3-hydroxy-5-t-butyloxycarbonylamino-1,6-diphenylhexane×0.5 succinate (111.9 g, 0.25 mol) was charged to a 2L, 3-necked round-bottomed flask with mechanical stirring. NaHCO3 (106 g, 1.26 mol), 600 ml H2O and 600 ml EtOAc were added and stirred vigorously until all solids were dissolved (15 minutes). Stirring was slowed and a solution of the 2,6-dimethyl-phenoxyacetyl chloride and EtOAc (100 ml) was added in a narrow stream via addition funnel. After 30 min of stirring, starting materials were consumed (HPLC analysis) and the layers were separated. The aqueous layer was extracted with EtOAc, the organic layers were combined and washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine, dried over MgSO4, filtered and concentrated to provide the desired product as a white solid. were dissolved (15 minutes) Stirring After 30 min of stirring were consumed (HPLC analysis) the layers were separated The aqueous layer was extracted with EtOAc washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine dried over MgSO4 filtered concentrated

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

実験手順: [2S,3S,5S]-2-Amino-3-hydroxy-5-t-butyloxycarbonylamino-1,6-diphenylhexane×0.5 succinate (111.9 g, 0.25 mol) was charged to a 2L, 3-necked round-bottomed flask with mechanical stirring. NaHCO3 (106 g, 1.26 mol), 600 ml H2Q and 600 ml EtOAc were added and stirred vigorously until all solids were dissolved (15 minutes). Stirring was slowed and a solution of the 2,6-dimethyl-phenoxyacetyl chloride and EtOAc (100 ml) was added in a narrow stream via addition funnel. After 30 min of stirring, starting materials were consumed (HPLC analysis) and the layers were separated. The aqueous layer was extracted With EtOAc, the organic layers were combined and washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine, dried over MgSO4 filtered and concentrated to provide the desired product as a white solid. were dissolved (15 minutes) Stirring After 30 min of stirring were consumed (HPLC analysis) the layers were separated The aqueous layer was extracted With EtOAc washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine dried over MgSO4 filtered concentrated

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

実験手順: [2S,3S,5S]-2-Amino-3-hydroxy-5-t-butyloxycarbonylamino-1,6-diphenylhexane×0.5 succinate (111.9 g, 0.25 mol) was charged to a 2L, 3-necked round-bottomed flask with mechanical stirring. NaHCO3 (106 g, 1.26 mol), 600 ml H2Q and 600 ml EtOAc were added and stirred vigorously until all solids were dissolved (15 minutes). Stirring was slowed and a solution of the 2,6-dimethyl-phenoxyacetyl chloride and EtOAc (100 ml) was added in a narrow stream via addition funnel. After 30 min of stirring, starting materials were consumed (HPLC analysis) and the layers were separated. The aqueous layer was extracted With EtOAc, the organic layers were combined and washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine, dried over MgSO4 filtered and concentrated to provide the desired product as a white solid. were dissolved (15 minutes) Stirring After 30 min of stirring were consumed (HPLC analysis) the layers were separated The aqueous layer was extracted With EtOAc washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine dried over MgSO4 filtered concentrated

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

実験手順: [2S,3S,5S]-2-Amino-3-hydroxy-5-t-butyloxycarbonylamino-1,6-diphenylhexane×0.5 succinate (111.9 g, 0.25 mol) was charged to a 2L, 3-necked round-bottomed flask with mechanical stirring. NaHCO3 (106 g, 1.26 mol), 600 ml H2Q and 600 ml EtOAc were added and stirred vigorously until all solids were dissolved (15 minutes). Stirring was slowed and a solution of the 2,6-dimethyl-phenoxyacetyl chloride and EtOAc (100 ml) was added in a narrow stream via addition funnel. After 30 min of stirring, starting materials were consumed (HPLC analysis) and the layers were separated. The aqueous layer was extracted With EtOAc, the organic layers were combined and washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine, dried over MgSO4 filtered and concentrated to provide the desired product as a white solid. were dissolved (15 minutes) Stirring After 30 min of stirring were consumed (HPLC analysis) the layers were separated The aqueous layer was extracted With EtOAc washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine dried over MgSO4 filtered concentrated

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

実験手順: Oxallyl chloride (36.3 ml, 0.42 mol) was added to a slurry of 2-6 dimethylphenoxyacetic acid (50 g, 0.28 mol) in 500 ml toluene followed by addition of 5 drops of DMF and stirred at room temperature for 30 min, then at 55° C. for 1.5 hours. The toluene was removed on a rotary evaporator and remaining volatiles were removed in vacuo to afford 2,6-dimethylphenoxyacetyl chloride as an amber oil, 55 grams, 100%. [2S,3S,5S]-2-Amino-3-hydroxy-5-t-butyloxycarbonylamino-1,6-diphenylhexane×0.5 succinate (111.9 g, 0.25 mol) was charged to a 2 L, 3-necked round-bottomed flask with mechanical stirring. NaHCO3 (106 9, 1.26 mol), 600 ml H2O and 600 ml EtOAc were added and stirred vigorously until all solids were dissolved (15 minutes). Stirring was slowed and a solution of the 2,6-dimethyl-phenoxyacetyl chloride and EtOAc (100 ml) was added in a narrow stream via addition funnel. After 30 min of stirring, starting materials were consumed (HPLC analysis) and the layers were separated. The aqueous layer was extracted with EtOAc, the organic layers were combined and washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine, dried over MgSO4, filtered and concentrated to provide the desired product as a white solid. were dissolved (15 minutes) Stirring After 30 min of stirring were consumed (HPLC analysis) the layers were separated The aqueous layer was extracted with EtOAc washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine dried over MgSO4 filtered concentrated

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,6-dimethylphenoxyacetylchloride is prepared in a separate vessel as follows: 2,6-dimethylphenoxyacetic acid, 5.4060 grams (29.99 mmol) is charged to a 50 mL round bottom flask equipped with a teflon-coated magnetic stir bar. Toluene, 15 mL is added stirring is initiated and thionyl chloride, 9.0 mL (123.3 mmol) is added followed by one drop of N,N-dimethylformamide at ambient temperature. After seven hours, the reaction mixture is heated to 65° C. for thirty minutes and allowed to cool to ambient temperature. The solution is concentrated at 60° C. and ca. 60 mm Hg pressure to remove all volatiles. The residue is diluted with toluene, 25 mL and reconcentrated. This is repeated a second time to give a final residue. equipped with a teflon-coated magnetic stir bar to cool to ambient temperature The solution is concentrated at 60° C. ca. 60 mm Hg pressure to remove all volatiles The residue is diluted with toluene, 25 mL

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

実験手順: [2S,3S,5S]-2-Amino-3-hydroxy-5-t-butyloxycarbonylamino-1,6-diphenylhexane×0.5 succinate (111.9 g, 0.25 mol) was charged to a 2L, 3-necked round-bottomed flask with mechanical stirring. NaHCO3 (106 g, 1.26 mol), 600 ml H2O and 600 ml EtOAc were added and stirred vigorously until all solids were dissolved (15 minutes). Stirring was slowed and a solution of the 2,6-dimethyl-phenoxyacetyl chloride and EtOAc (100 ml) was added in a narrow stream via addition funnel. After 30 min of stirring, starting materials were consumed (HPLC analysis) and the layers were separated. The aqueous layer was extracted with EtOAc, the organic layers were combined and washed with 200 ml of 1M NaOH, 200 ml of 10% HCl, 200 ml of brine, dried over MgSO4, filtered and concentrated to provide the desired product as a white solid. were dissolved (15 minutes) Stirring After 30 min of stirring were consumed (HPLC analysis) the layers were separated The aqueous layer was extracted with EtOAc washed with 200 ml of 1M NaOH, 200 ml of 10% HCl, 200 ml of brine dried over MgSO4 filtered concentrated

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

実験手順: [2S,3S,5S]-2-Amino-3-hydroxy-5-t-butyloxycarbonylamino-1,6-diphenylhexane×0.5 succinate (111.9 g, 0.25 mol) was charged to a 2L, 3-necked round-bottomed flask with mechanical stirring. NaHCO3 (106 g, 1.26 mol), 600 ml H2O and 600 ml EtOAc were added and stirred vigorously until all solids were dissolved (15 minutes). Stirring was slowed and a solution of the 2,6-dimethyl-phenoxyacetyl chloride and EtOAc (100 ml) was added in a narrow stream via addition funnel. After 30 min of stirring, starting materials were consumed (HPLC analysis) and the layers were separated. The aqueous layer was extracted with EtOAc, the organic layers were combined and washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine, dried over MgSO4, filtered and concentrated to provide the desired product as a white solid. were dissolved (15 minutes) Stirring After 30 min of stirring were consumed (HPLC analysis) the layers were separated The aqueous layer was extracted with EtOAc washed with 200 ml of 1 M NaOH, 200 ml of 10% HCl, 200 ml of brine dried over MgSO4 filtered concentrated