ethyl 3-amino-3-(4-chlorophenyl)propanoate

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: 5.70 g (25.0 mmol) of ethyl-3-amino-3-(4-chlorophenyl)propanoate [V. Wehner et al., Synthesis 14, 2023-2036 (2002)], 3.993 ml (27.5 mmol) of methyl 4-methyl-3-oxopentanoate and 2.87 ml (50.1 mmol) of acetic acid were taken up in 70 ml of benzene and reacted at reflux on a water separator overnight. After cooling, the mixture was washed with saturated aqueous sodium bicarbonate solution, the organic phase was dried with magnesium sulfate and the solvent was destilled off under reduced pressure. This gave 8.57 g (68% of theory) of the target compound in a purity of 70%. The fraction was used without further work-up for the subsequent steps. reacted After cooling the mixture was washed with saturated aqueous sodium bicarbonate solution the organic phase was dried with magnesium sulfate

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

実験手順: 10 g (71.1 mmol) of 4-chlorobenzaldehyde, 9.40 g (71.1 mmol) of monoethyl malonate and 10.9 g (142.3 mmol) of ammonium acetate were taken up in 60 ml of ethanol, and the mixture was stirred at reflux temperature overnight. After cooling, 50 ml 1N hydrochloric acid were added to the residue and the mixture was washed with ethyl acetate. The aqueous phase was made basic with potassium carbonate and then extracted with dichloromethane (2×). The organic phase was dried with magnesium sulfate and the solvent was removed on a rotary evaporator. The residue was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 10:90→90:10). This gave 1.80 g (11% of theory) of the target compound. at reflux temperature overnight After cooling the mixture was washed with ethyl acetate extracted with dichloromethane (2×) The organic phase was dried with magnesium sulfate the solvent was removed on a rotary evaporator The residue was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 10:90→90:10)

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

実験手順: 10 g (71.1 mmol) of 4-chlorobenzaldehyde, 9.40 g (71.1 mmol) of monoethyl malonate and 10.9 g (142.3 mmol) of ammonium acetate were taken up in 60 ml of ethanol, and the mixture was stirred at reflux temperature overnight. After cooling, 50 ml 1N hydrochloric acid were added to the residue and the mixture was washed with ethyl acetate. The aqueous phase was made basic with potassium carbonate and then extracted with dichloromethane (2×). The organic phase was dried with magnesium sulfate and the solvent was removed on a rotary evaporator. The residue was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 10:90→90:10). This gave 1.80 g (11% of theory) of the target compound. at reflux temperature overnight After cooling the mixture was washed with ethyl acetate extracted with dichloromethane (2×) The organic phase was dried with magnesium sulfate the solvent was removed on a rotary evaporator The residue was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 10:90→90:10)

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

実験手順: Following procedures outlined in Example 1 step 1 is accomplished with 3-Amino-3-(4-chloro-phenyl)-propionic acid ethyl ester (5.2) and Intermediate 4.1 then using 2-methyl-propionaldehyde (3.1) in step 2 after acidic hydrolysis and purification the title compound is isolated as a white foam. Molecular Formula=C27H33ClN2O6; (M+H)+=517; Rt=2.53 min (A), purity 98.8%.

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: Following procedures outlined in Example 1 step 1 is accomplished with 3-Amino-3-(4-chloro-phenyl)-propionic acid ethyl ester (5.2) and Intermediate 4.1 then using 2-methyl-propionaldehyde (3.1) in step 2 after acidic hydrolysis and purification the title compound is isolated as a white foam. Molecular Formula=C27H33ClN2O6; (M+H)+=517; Rt=2.53 min (A), purity 98.8%.

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: 5.70 g (25.0 mmol) of ethyl-3-amino-3-(4-chlorophenyl)propanoate [V. Wehner et al., Synthesis 14, 2023-2036 (2002)], 3.993 ml (27.5 mmol) of methyl 4-methyl-3-oxopentanoate and 2.87 ml (50.1 mmol) of acetic acid were taken up in 70 ml of benzene and reacted at reflux on a water separator overnight. After cooling, the mixture was washed with saturated aqueous sodium bicarbonate solution, the organic phase was dried with magnesium sulfate and the solvent was destilled off under reduced pressure. This gave 8.57 g (68% of theory) of the target compound in a purity of 70%. The fraction was used without further work-up for the subsequent steps. reacted After cooling the mixture was washed with saturated aqueous sodium bicarbonate solution the organic phase was dried with magnesium sulfate

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

実験手順: 10 g (71.1 mmol) of 4-chlorobenzaldehyde, 9.40 g (71.1 mmol) of monoethyl malonate and 10.9 g (142.3 mmol) of ammonium acetate were taken up in 60 ml of ethanol, and the mixture was stirred at reflux temperature overnight. After cooling, 50 ml 1N hydrochloric acid were added to the residue and the mixture was washed with ethyl acetate. The aqueous phase was made basic with potassium carbonate and then extracted with dichloromethane (2×). The organic phase was dried with magnesium sulfate and the solvent was removed on a rotary evaporator. The residue was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 10:90→90:10). This gave 1.80 g (11% of theory) of the target compound. at reflux temperature overnight After cooling the mixture was washed with ethyl acetate extracted with dichloromethane (2×) The organic phase was dried with magnesium sulfate the solvent was removed on a rotary evaporator The residue was purified by preparative HPLC (mobile phase: acetonitrile/water, gradient 10:90→90:10)

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

実験手順: Following procedures outlined in Example 1 step 1 is accomplished with 3-Amino-3-(4-chloro-phenyl)-propionic acid ethyl ester (5.2) and Intermediate 4.1 then using 2-methyl-propionaldehyde (3.1) in step 2 after acidic hydrolysis and purification the title compound is isolated as a white foam. Molecular Formula=C27H33ClN2O6; (M+H)+=517; Rt=2.53 min (A), purity 98.8%.