methyl 3-oxo-3-phenylpropanoate

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:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Benzofurazancarboxaldehyde (2.96 g, 20 mmoles), methyl beta-oxobenzenepropanoate (3.56 g, 20 mmoles), piperidine (0.05 ml) and hexanoic acid (0.13 ml) were heated at reflux for 3 hours in benzene (50 ml) using a Dean and Stark apparatus. The reaction was cooled, diluted with ethyl acetate and washed in turn with water, brine and saturated sodium bicarbonate and dried (Na2SO4). The solvent was removed in vacuo and the residue dissolved in ethanol (6 ml). 1-Methylethyl 3-amino-2-butenoate (3.0 g) and diethylamine (0.6 ml) were added and the mixture heated at 60° for 34 hours. The reaction mixture was cooled, evaporated to dryness in vacuo and the residue was dissolved in 2-propanol and treated with charcoal. The charcoal was filtered off and the title compound (1.1 g) was obtained on addition of cyclohexane mp 132°-4°. The reaction was cooled washed in turn with water, brine and saturated sodium bicarbonate dried (Na2SO4) The solvent was removed in vacuo the residue dissolved in ethanol (6 ml) 1-Methylethyl 3-amino-2-butenoate (3.0 g) and diethylamine (0.6 ml) were added the mixture heated at 60° for 34 hours The reaction mixture was cooled evaporated to dryness in vacuo the residue was dissolved in 2-propanol treated with charcoal The charcoal was filtered off

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: A 1-L flask fitted with a mechanical stirrer, reflux condenser, and nitrogen sweep (to protect the Na), was immersed in a water bath to control temperature (i.e., to provide heat and to cool if need be). In the flask was placed 272.3 g (2 moles) of methyl benzoate; 74.1 g (1 mole) of methyl acetate; 1 gm. atom--23 g., Na; and 32 g (1 mole) of methanol (to react with the Na and to initate the reaction). The flask was purged with nitrogen and was maintained under a positive nitrogen pressure throughout the reaction. The solution was heated to 80°-85° C. overnight, during which time all the Na metal was consumed. The resulting yellow heterogeneous solution was cooled to room temperature and poured into a separatory funnel containing 130 ml of concentrated hydrochloric acid and 200 g. of crushed ice. This was shaken and the lower aqueous phase removed. (In this step the Na in the Na methyl benzoyl acetate reacts with the HC1 and is removed as NaCl.) The residual material was then washed with water, 2×100 mls, saturated NaHCO3 solution, 2×100 mls. and finally 2×100 mls of saturated brine (NaCl). (Byproduct methanol leaves with the water in the water washes). The residual yellow organic phase was then transferred to a distilling flask and fractionated through a 12-inch Vigreux column at 0.5 mm Hg pressure. A forerum containing methyl benzoate and methyl acetoacetate was collected at 37°-42° C. at 0.5 mm Hg. This was followed by a fraction of 82.5 methyl benzoyl acetate boiling at 81°-84° C. at 0.5 mm Hg. Yield of the pure product methyl benzoyl acetate based on Na was 46.3%, as a water white liquid. A 1-L flask fitted with a mechanical stirrer reflux condenser was immersed in a water bath to control temperature (i.e., to provide heat and to cool if need be) the reaction) The flask was purged with nitrogen was maintained under a positive nitrogen pressure throughout the reaction was consumed poured into a separatory funnel containing 130 ml of concentrated hydrochloric acid and 200 g the lower aqueous phase removed (In this step the Na in the Na methyl benzoyl acetate reacts with the HC1 is removed as NaCl ) The residual material was then washed with water, 2×100 mls, saturated NaHCO3 solution, 2×100 mls (Byproduct methanol leaves with the water in the water washes) The residual yellow organic phase was then transferred to a distilling flask was collected at 37°-42° C. at 0.5 mm Hg

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

実験手順: 4-Benzofurazancarboxaldehyde (2.96 g, 20 mmoles), methyl beta-oxobenzenepropanoate (3.56 g, 20 mmoles), piperidine (0.05 ml) and hexanoic acid (0.13 ml) were heated at reflux for 3 hours in benzene (50 ml) using a Dean and Stark apparatus. The reaction was cooled, diluted with ethyl acetate and washed in turn with water, brine and saturated sodium bicarbonate and dried (Na2SO4). The solvent was removed in vacuo and the residue dissolved in ethanol (6 ml). 1-Methylethyl 3-amino-2-butenoate (3.0 g) and diethylamine (0.6 ml) were added and the mixture heated at 60° for 34 hours. The reaction mixture was cooled, evaporated to dryness in vacuo and the residue was dissolved in 2-propanol and treated with charcoal. The charcoal was filtered off and the title compound (1.1 g) was obtained on addition of cyclohexane mp 132°-4°. The reaction was cooled washed in turn with water, brine and saturated sodium bicarbonate dried (Na2SO4) The solvent was removed in vacuo the residue dissolved in ethanol (6 ml) 1-Methylethyl 3-amino-2-butenoate (3.0 g) and diethylamine (0.6 ml) were added the mixture heated at 60° for 34 hours The reaction mixture was cooled evaporated to dryness in vacuo the residue was dissolved in 2-propanol treated with charcoal The charcoal was filtered off

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

実験手順: 4-Benzofurazancarboxaldehyde (2.96 g, 20 mmoles), methyl beta-oxobenzenepropanoate (3.56 g, 20 mmoles), piperidine (0.05 ml) and hexanoic acid (0.13 ml) were heated at reflux for 3 hours in benzene (50 ml) using a Dean and Stark apparatus. The reaction was cooled, diluted with ethyl acetate and washed in turn with water, brine and saturated sodium bicarbonate and dried (Na2SO4). The solvent was removed in vacuo and the residue dissolved in ethanol (6 ml). 1-Methylethyl 3-amino-2-butenoate (3.0 g) and diethylamine (0.6 ml) were added and the mixture heated at 60° for 34 hours. The reaction mixture was cooled, evaporated to dryness in vacuo and the residue was dissolved in 2-propanol and treated with charcoal. The charcoal was filtered off and the title compound (1.1 g) was obtained on addition of cyclohexane mp 132°-4°. The reaction was cooled washed in turn with water, brine and saturated sodium bicarbonate dried (Na2SO4) The solvent was removed in vacuo the residue dissolved in ethanol (6 ml) 1-Methylethyl 3-amino-2-butenoate (3.0 g) and diethylamine (0.6 ml) were added the mixture heated at 60° for 34 hours The reaction mixture was cooled evaporated to dryness in vacuo the residue was dissolved in 2-propanol treated with charcoal The charcoal was filtered off

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:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ru(OAc)2((R)-dm-binap) (13.4 mg, 0.0140 mmol), methyl benzoylacetate (500 mg, 2.806 mmol), ammonium acetate (216 mg, 2.806 mmol) and methanol (2.5 mL) were placed in a 100 mL stainless steel autoclave under nitrogen atmosphere, and the mixture was stirred at 80° C. for 1 hour. The reaction mixture was cooled down to room temperature and further stirred under a hydrogen pressure of 3 MPa at 80° C. for 15 hours. After completion of the reaction, the solvent was removed by evaporation and the residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate/triethylamine=50/50/5-0/95/5) to give methyl (3S)-3-amino-3-phenylpropionate (201 mg) as a colorless oil in 40.0% yield. The enantiomeric excess of the product was determined to be 96.7% ee by HPLC analysis using a SUMICHIRAL OA-4100R column (available from SUMIKA CHEMICAL ANALYSIS SERVICE LTD.) after conversion into methyl (3S)-3-(4-nitrobenzoylamino)-3-phenylpropionate. The reaction mixture was cooled down to room temperature further stirred under a hydrogen pressure of 3 MPa at 80° C. for 15 hours After completion of the reaction the solvent was removed by evaporation the residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate/triethylamine=50/50/5-0/95/5)

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

実験手順: A 1-I flask fitted with a mechanical stirrer, reflux condenser, and nitrogen sweep (to protect the Na), was immersed in a water bath to control temperature (i.e., to provide heat and to cool if need be). In the flask was placed 272.3 g (2 moles) of methyl benzoate; 74.1 g (1 mole) of methyl acetate; 1 gm. atom--23 g., Na; and 32 g (1 mole) of methanol (to react with the Na and to initiate the reaction). The flask was purged with nitrogen and was maintained under a positive nitrogen pressure throughout the reaction. The solution was heated to 80°-85° C. overnight, during which time all the Na metal was consumed. The resulting yellow heterogeneous solution was cooled to room temperature and poured into a separatory funnel containing 130 ml of concentrated hydrochloric acid and 200 g. of crushed ice. This was shaken and the lower aqueous phase removed. (In this step the Na in the Na methyl benzoyl acetate reacts with the HCl and is removed as NaCl.) The residual material was then washed with water, 2×100 mls, saturated NaHCO3 olution, 2×100 mls, and finally 2×100 mls of saturated brine (NaCl). (Byproduct methanol leaves with the water in the water washes.) The residual yellow organic phase was then transferred to a distilling flask and fractionated through a 12-inch Vigreux column at 0.5 mm Hg pressure. A forerun containing methyl benzoate and methyl acetoacetate was collected at 37°-42° C. at 0.5 mm Hg. This was followed by a fraction of 82.5 g. methyl benzoyl acetate boiling at 81°-84° C. at 0.5 mm Hg. Yield of the pure product methyl benzoyl acetate based on Na was 46.3%, as a water white liquid. A 1-I flask fitted with a mechanical stirrer reflux condenser was immersed in a water bath to control temperature (i.e., to provide heat and to cool if need be) the reaction) The flask was purged with nitrogen was maintained under a positive nitrogen pressure throughout the reaction was consumed poured into a separatory funnel containing 130 ml of concentrated hydrochloric acid and 200 g the lower aqueous phase removed (In this step the Na in the Na methyl benzoyl acetate reacts with the HCl is removed as NaCl ) The residual material was then washed with water, 2×100 mls, saturated NaHCO3 olution, 2×100 mls, and finally 2×100 mls of saturated brine (NaCl) (Byproduct methanol leaves with the water in the water washes ) The residual yellow organic phase was then transferred to a distilling flask was collected at 37°-42° C. at 0.5 mm Hg