Ethyl 3-(((benzyloxy)carbonyl)-(2-ethoxy-2-oxoethyl)amino)propanoate

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: To a suspension of potassium t-butoxide (2.52 g, 22.4 mmol, 1.4 equiv.) in toluene (50 mL) at 0° C. under nitrogen, was added diester 70 (5.41 g, 16 mmol) in toluene (10 mL) over a 10 min period. The solution was stirred for 30 min at 0° C. and 2 mL of glacial acetic acid was added, immediately followed by 10 g of NaH2PO4.H2O in 100 mL of ice-cold water. The resultant mixture was extracted with chloroform (3×150 mL), and the combined organic extracts were washed twice with phosphate buffer (2×25 mL, pH=7.0), dried over anhydrous sodium sulfate and evaporated to dryness. The residue was dissolved in toluene (200 mL), cooled to 0° C., and extracted with cold pH 9.5 carbonate buffer (3×150 mL). The aqueous extracts were converted to pH 3 with phosphoric acid, and extracted with chloroform (5×125 mL) which were combined, dried, and evaporated to a afford keto ester 71 (2.2 g, 42%). The resultant mixture was extracted with chloroform (3×150 mL) the combined organic extracts were washed twice with phosphate buffer (2×25 mL, pH=7.0) dried over anhydrous sodium sulfate evaporated to dryness The residue was dissolved in toluene (200 mL) cooled to 0° C. extracted with cold pH 9.5 carbonate buffer (3×150 mL) extracted with chloroform (5×125 mL) which dried evaporated to a afford keto ester 71 (2.2 g, 42%)

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

実験手順: To a suspension of potassium t-butoxide (2.52 g, 22.4 mmol, 1.4 equiv.) in toluene (50 mL) at 0° C. under nitrogen, was added diester 70 (5.41 g, 16 mmol) in toluene (10 mL) over a 10 min period. The solution was stirred for 30 min at 0° C. and 2 mL of glacial acetic acid was added, immediately followed by 10 g of NaH2PO4.H2O in 100 mL of ice-cold water. The resultant mixture was extracted with chloroform (3×150 mL), and the combined organic extracts were washed twice with phosphate buffer (2×25 mL, pH=7.0), dried over anhydrous sodium sulfate and evaporated to dryness. The residue was dissolved in toluene (200 mL), cooled to 0° C., and extracted with cold pH 9.5 carbonate buffer (3×150 mL). The aqueous extracts were converted to pH 3 with phosphoric acid, and extracted with chloroform (5×125 mL) which were combined, dried, and evaporated to a afford keto ester 71 (2.2 g, 42%). The resultant mixture was extracted with chloroform (3×150 mL) the combined organic extracts were washed twice with phosphate buffer (2×25 mL, pH=7.0) dried over anhydrous sodium sulfate evaporated to dryness The residue was dissolved in toluene (200 mL) cooled to 0° C. extracted with cold pH 9.5 carbonate buffer (3×150 mL) extracted with chloroform (5×125 mL) which dried evaporated to a afford keto ester 71 (2.2 g, 42%)

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

実験手順: To a solution of diester 58 (3.88 g, 20.2 mmol) in dry acetonitrile (40 mL) at 0° C., under Argon, was added slowly benzyl chloroformate (3.17 mL, 1.1 equiv.). The solution was stirred at 0° C. for 1 h after which it was poured into water (50 mL). The phases were separated and the aqueous layer was extracted with dichloromethane (3×50 mL). the combined organic extracts were washed with 5% HCl, water, brine and dried over anhydrous sodium sulfate. Evaporation of the solvents was followed by distillation to afford compound 70 as a colorless oil (5.4 g, 80%). The phases were separated the aqueous layer was extracted with dichloromethane (3×50 mL) the combined organic extracts were washed with 5% HCl, water, brine dried over anhydrous sodium sulfate Evaporation of the solvents was followed by distillation

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of glycine ethyl ester hydrochloride (41.9 g, 0.3 mol) in ethanol (300 mL) was added triethylamine (41.8 mL, 0.3 mol) and ethyl acrylate (10.8 mL, 0.1 mol) in an ice bath, and the mixture was stirred at 80° C. for 1 hour. The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue, and the mixture was extracted with ethyl acetate (200 mL×3). The extract was washed with water (200 mL×2) and saturated aqueous solution of sodium chloride (200 mL) in this order, an the dried with anhydrous sodium sulfate. After the filtration, the filtrate was concentrated under reduced pressure, and the residue was dissolved in acetone (150 mL). To this solution were added aqueous solution of sodium carbonate (11.5 g, 108 mmol) (50 mL) and a solution of benzyloxycarbonyl chloride (18.4 g, 108 mmol) in acetone (50 mL) in an ice bath, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue. The mixture was extracted with ethyl acetate (200 mL×3), and the extract was washed with saturated aqueous solution of sodium chloride (200 mL), and dried with anhydrous sodium sulfate. After the filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate, 5:1) to obtain 31.1 g (92%) of the title compound as a colorless oily product. The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue the mixture was extracted with ethyl acetate (200 mL×3) The extract was washed with water (200 mL×2) and saturated aqueous solution of sodium chloride (200 mL) in this order an the dried with anhydrous sodium sulfate After the filtration the filtrate was concentrated under reduced pressure the residue was dissolved in acetone (150 mL) The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue The mixture was extracted with ethyl acetate (200 mL×3) the extract was washed with saturated aqueous solution of sodium chloride (200 mL) dried with anhydrous sodium sulfate After the filtration the filtrate was concentrated under reduced pressure the residue was purified by silica gel column chromatography (hexane:ethyl acetate, 5:1)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of glycine ethyl ester hydrochloride (41.9 g, 0.3 mol) in ethanol (300 mL) was added triethylamine (41.8 mL, 0.3 mol) and ethyl acrylate (10.8 mL, 0.1 mol) in an ice bath, and the mixture was stirred at 80° C. for 1 hour. The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue, and the mixture was extracted with ethyl acetate (200 mL×3). The extract was washed with water (200 mL×2) and saturated aqueous solution of sodium chloride (200 mL) in this order, an the dried with anhydrous sodium sulfate. After the filtration, the filtrate was concentrated under reduced pressure, and the residue was dissolved in acetone (150 mL). To this solution were added aqueous solution of sodium carbonate (11.5 g, 108 mmol) (50 mL) and a solution of benzyloxycarbonyl chloride (18.4 g, 108 mmol) in acetone (50 mL) in an ice bath, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue. The mixture was extracted with ethyl acetate (200 mL×3), and the extract was washed with saturated aqueous solution of sodium chloride (200 mL), and dried with anhydrous sodium sulfate. After the filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate, 5:1) to obtain 31.1 g (92%) of the title compound as a colorless oily product. The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue the mixture was extracted with ethyl acetate (200 mL×3) The extract was washed with water (200 mL×2) and saturated aqueous solution of sodium chloride (200 mL) in this order an the dried with anhydrous sodium sulfate After the filtration the filtrate was concentrated under reduced pressure the residue was dissolved in acetone (150 mL) The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue The mixture was extracted with ethyl acetate (200 mL×3) the extract was washed with saturated aqueous solution of sodium chloride (200 mL) dried with anhydrous sodium sulfate After the filtration the filtrate was concentrated under reduced pressure the residue was purified by silica gel column chromatography (hexane:ethyl acetate, 5:1)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of glycine ethyl ester hydrochloride (41.9 g, 0.3 mol) in ethanol (300 mL) was added triethylamine (41.8 mL, 0.3 mol) and ethyl acrylate (10.8 mL, 0.1 mol) in an ice bath, and the mixture was stirred at 80° C. for 1 hour. The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue, and the mixture was extracted with ethyl acetate (200 mL×3). The extract was washed with water (200 mL×2) and saturated aqueous solution of sodium chloride (200 mL) in this order, an the dried with anhydrous sodium sulfate. After the filtration, the filtrate was concentrated under reduced pressure, and the residue was dissolved in acetone (150 mL). To this solution were added aqueous solution of sodium carbonate (11.5 g, 108 mmol) (50 mL) and a solution of benzyloxycarbonyl chloride (18.4 g, 108 mmol) in acetone (50 mL) in an ice bath, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue. The mixture was extracted with ethyl acetate (200 mL×3), and the extract was washed with saturated aqueous solution of sodium chloride (200 mL), and dried with anhydrous sodium sulfate. After the filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate, 5:1) to obtain 31.1 g (92%) of the title compound as a colorless oily product. The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue the mixture was extracted with ethyl acetate (200 mL×3) The extract was washed with water (200 mL×2) and saturated aqueous solution of sodium chloride (200 mL) in this order an the dried with anhydrous sodium sulfate After the filtration the filtrate was concentrated under reduced pressure the residue was dissolved in acetone (150 mL) The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue The mixture was extracted with ethyl acetate (200 mL×3) the extract was washed with saturated aqueous solution of sodium chloride (200 mL) dried with anhydrous sodium sulfate After the filtration the filtrate was concentrated under reduced pressure the residue was purified by silica gel column chromatography (hexane:ethyl acetate, 5:1)

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

実験手順: To a suspension of potassium t-butoxide (2.52 g, 22.4 mmol, 1.4 equiv.) in toluene (50 mL) at 0° C. under nitrogen, was added diester 70 (5.41 g, 16 mmol) in toluene (10 mL) over a 10 min period. The solution was stirred for 30 min at 0° C. and 2 mL of glacial acetic acid was added, immediately followed by 10 g of NaH2PO4.H2O in 100 mL of ice-cold water. The resultant mixture was extracted with chloroform (3×150 mL), and the combined organic extracts were washed twice with phosphate buffer (2×25 mL, pH=7.0), dried over anhydrous sodium sulfate and evaporated to dryness. The residue was dissolved in toluene (200 mL), cooled to 0° C., and extracted with cold pH 9.5 carbonate buffer (3×150 mL). The aqueous extracts were converted to pH 3 with phosphoric acid, and extracted with chloroform (5×125 mL) which were combined, dried, and evaporated to a afford keto ester 71 (2.2 g, 42%). The resultant mixture was extracted with chloroform (3×150 mL) the combined organic extracts were washed twice with phosphate buffer (2×25 mL, pH=7.0) dried over anhydrous sodium sulfate evaporated to dryness The residue was dissolved in toluene (200 mL) cooled to 0° C. extracted with cold pH 9.5 carbonate buffer (3×150 mL) extracted with chloroform (5×125 mL) which dried evaporated to a afford keto ester 71 (2.2 g, 42%)

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

実験手順: To a solution of diester 58 (3.88 g, 20.2 mmol) in dry acetonitrile (40 mL) at 0° C., under Argon, was added slowly benzyl chloroformate (3.17 mL, 1.1 equiv.). The solution was stirred at 0° C. for 1 h after which it was poured into water (50 mL). The phases were separated and the aqueous layer was extracted with dichloromethane (3×50 mL). the combined organic extracts were washed with 5% HCl, water, brine and dried over anhydrous sodium sulfate. Evaporation of the solvents was followed by distillation to afford compound 70 as a colorless oil (5.4 g, 80%). The phases were separated the aqueous layer was extracted with dichloromethane (3×50 mL) the combined organic extracts were washed with 5% HCl, water, brine dried over anhydrous sodium sulfate Evaporation of the solvents was followed by distillation

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of glycine ethyl ester hydrochloride (41.9 g, 0.3 mol) in ethanol (300 mL) was added triethylamine (41.8 mL, 0.3 mol) and ethyl acrylate (10.8 mL, 0.1 mol) in an ice bath, and the mixture was stirred at 80° C. for 1 hour. The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue, and the mixture was extracted with ethyl acetate (200 mL×3). The extract was washed with water (200 mL×2) and saturated aqueous solution of sodium chloride (200 mL) in this order, an the dried with anhydrous sodium sulfate. After the filtration, the filtrate was concentrated under reduced pressure, and the residue was dissolved in acetone (150 mL). To this solution were added aqueous solution of sodium carbonate (11.5 g, 108 mmol) (50 mL) and a solution of benzyloxycarbonyl chloride (18.4 g, 108 mmol) in acetone (50 mL) in an ice bath, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue. The mixture was extracted with ethyl acetate (200 mL×3), and the extract was washed with saturated aqueous solution of sodium chloride (200 mL), and dried with anhydrous sodium sulfate. After the filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate, 5:1) to obtain 31.1 g (92%) of the title compound as a colorless oily product. The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue the mixture was extracted with ethyl acetate (200 mL×3) The extract was washed with water (200 mL×2) and saturated aqueous solution of sodium chloride (200 mL) in this order an the dried with anhydrous sodium sulfate After the filtration the filtrate was concentrated under reduced pressure the residue was dissolved in acetone (150 mL) The reaction mixture was concentrated under reduced pressure, and water (400 mL) was added to the residue The mixture was extracted with ethyl acetate (200 mL×3) the extract was washed with saturated aqueous solution of sodium chloride (200 mL) dried with anhydrous sodium sulfate After the filtration the filtrate was concentrated under reduced pressure the residue was purified by silica gel column chromatography (hexane:ethyl acetate, 5:1)

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

実験手順: To a suspension of potassium t-butoxide (2.52 g, 22.4 mmol, 1.4 equiv.) in toluene (50 mL) at 0° C. under nitrogen, was added diester 70 (5.41 g, 16 mmol) in toluene (10 mL) over a 10 min period. The solution was stirred for 30 min at 0° C. and 2 mL of glacial acetic acid was added, immediately followed by 10 g of NaH2PO4.H2O in 100 mL of ice-cold water. The resultant mixture was extracted with chloroform (3×150 mL), and the combined organic extracts were washed twice with phosphate buffer (2×25 mL, pH=7.0), dried over anhydrous sodium sulfate and evaporated to dryness. The residue was dissolved in toluene (200 mL), cooled to 0° C., and extracted with cold pH 9.5 carbonate buffer (3×150 mL). The aqueous extracts were converted to pH 3 with phosphoric acid, and extracted with chloroform (5×125 mL) which were combined, dried, and evaporated to a afford keto ester 71 (2.2 g, 42%). The resultant mixture was extracted with chloroform (3×150 mL) the combined organic extracts were washed twice with phosphate buffer (2×25 mL, pH=7.0) dried over anhydrous sodium sulfate evaporated to dryness The residue was dissolved in toluene (200 mL) cooled to 0° C. extracted with cold pH 9.5 carbonate buffer (3×150 mL) extracted with chloroform (5×125 mL) which dried evaporated to a afford keto ester 71 (2.2 g, 42%)

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

実験手順: To a solution of diester 58 (3.88 g, 20.2 mmol) in dry acetonitrile (40 mL) at 0° C., under Argon, was added slowly benzyl chloroformate (3.17 mL, 1.1 equiv.). The solution was stirred at 0° C. for 1 h after which it was poured into water (50 mL). The phases were separated and the aqueous layer was extracted with dichloromethane (3×50 mL). the combined organic extracts were washed with 5% HCl, water, brine and dried over anhydrous sodium sulfate. Evaporation of the solvents was followed by distillation to afford compound 70 as a colorless oil (5.4 g, 80%). The phases were separated the aqueous layer was extracted with dichloromethane (3×50 mL) the combined organic extracts were washed with 5% HCl, water, brine dried over anhydrous sodium sulfate Evaporation of the solvents was followed by distillation