ethyl 3-anilino-3-oxopropanoate

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

Procedure: Ethyl 3-oxo-3-(phenylamino)propionate (56.8 g, 0.27 mol) and 4-methoxy-3-buten-2-one (30.2 g, 0.30 mol) were dissolved in methanol (300 mL), and 20% sodium ethoxide. (112 g, 0.33 mol) was added dropwise thereto at room temperature. After the dropwise addition, the mixture was refluxed for 8 hours under heating. The reaction mixture was cooled and then concentrated under reduced pressure, and thus obtained residue was dissolved in a mixed solution of 1,4-dioxane (200 mL) and water (200 mL). To the resultant solution, lithium hydroxide monohydrate (23.0 g, 0.55 mol) was added, and the mixture was stirred overnight at room temperature. The reaction mixture was poured into water, and washed with ethyl acetate. The aqueous layer was acidified by adding citric acid, and then extracted with chloroform. The organic layer was washed with water, dried, and concentrated, and thus obtained crystal was washed with ethyl acetate, to obtain 43.4 g of a desired product (yield: 69%). (112 g, 0.33 mol) was added dropwise at room temperature After the dropwise addition the mixture was refluxed for 8 hours under heating The reaction mixture was cooled concentrated under reduced pressure, and thus obtained residue was dissolved in a mixed solution of 1,4-dioxane (200 mL) and water (200 mL) washed with ethyl acetate by adding citric acid extracted with chloroform The organic layer was washed with water dried concentrated thus obtained crystal was washed with ethyl acetate

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

Procedure: Ethyl malonyl chloride (15.1 g, 0.10 mol) was added to a mixed solution of aniline (9.3 g, 0.10 mol), triethylamine (11.1 g, 0.11 mol), N,N-dimethylaminopyridine (1.5 g, 0.012 mol) and dichloromethane (300 mL), at 10° C. or below. This mixture was stirred for 3 hours at room temperature, and then poured into water. The organic layer was washed with diluted hydrochloric acid, aqueous saturated sodium bicarbonate and saturated brine, in this order. The obtained organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure, to obtain 19.5 g of a subject compound (yield: 94%). The organic layer was washed with diluted hydrochloric acid, aqueous saturated sodium bicarbonate and saturated brine, in this order The obtained organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure

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

Procedure: To a solution of sodium ethoxide in EtOH (prepared from sodium (0.5 g, 21.75 mmol) dissolved in EtOH (40 mL)) is added ethyl 3-oxo-3-(phenylamino)propanoate (4 g, 19.30 mmol) and trans-4-methoxy-3-buten-2-one (2 g, 19.98 mmol). After the reaction is stirred at reflux overnight, the mixture is concentrated. The residue is partitioned between H2O (50 mL) and EtOAc (50 mL). The aqueous layer is acidified with concentrated HCl to a pH 3˜4 and then it is extracted with EtOAc. The organic extracts are dried and concentrated. The residue is purified by silica gel column chromatography eluting with DCM:MeOH (25:1) to give the product (1.20 g, 27% yield). MS (m/z): 230.0 (M+H). at reflux overnight the mixture is concentrated The residue is partitioned between H2O (50 mL) and EtOAc (50 mL) it is extracted with EtOAc The organic extracts are dried concentrated The residue is purified by silica gel column chromatography eluting with DCM:MeOH (25:1)

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

Procedure: Ethyl 3-oxo-3-(phenylamino)propionate (56.8 g, 0.27 mol) and 4-methoxy-3-buten-2-one (30.2 g, 0.30 mol) were dissolved in methanol (300 mL), and 20% sodium ethoxide. (112 g, 0.33 mol) was added dropwise thereto at room temperature. After the dropwise addition, the mixture was refluxed for 8 hours under heating. The reaction mixture was cooled and then concentrated under reduced pressure, and thus obtained residue was dissolved in a mixed solution of 1,4-dioxane (200 mL) and water (200 mL). To the resultant solution, lithium hydroxide monohydrate (23.0 g, 0.55 mol) was added, and the mixture was stirred overnight at room temperature. The reaction mixture was poured into water, and washed with ethyl acetate. The aqueous layer was acidified by adding citric acid, and then extracted with chloroform. The organic layer was washed with water, dried, and concentrated, and thus obtained crystal was washed with ethyl acetate, to obtain 43.4 g of a desired product (yield: 69%). (112 g, 0.33 mol) was added dropwise at room temperature After the dropwise addition the mixture was refluxed for 8 hours under heating The reaction mixture was cooled concentrated under reduced pressure, and thus obtained residue was dissolved in a mixed solution of 1,4-dioxane (200 mL) and water (200 mL) washed with ethyl acetate by adding citric acid extracted with chloroform The organic layer was washed with water dried concentrated thus obtained crystal was washed with ethyl acetate

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

Procedure: To a solution of sodium ethoxide in EtOH (prepared from sodium (0.5 g, 21.75 mmol) dissolved in EtOH (40 mL)) is added ethyl 3-oxo-3-(phenylamino)propanoate (4 g, 19.30 mmol) and trans-4-methoxy-3-buten-2-one (2 g, 19.98 mmol). After the reaction is stirred at reflux overnight, the mixture is concentrated. The residue is partitioned between H2O (50 mL) and EtOAc (50 mL). The aqueous layer is acidified with concentrated HCl to a pH 3˜4 and then it is extracted with EtOAc. The organic extracts are dried and concentrated. The residue is purified by silica gel column chromatography eluting with DCM:MeOH (25:1) to give the product (1.20 g, 27% yield). MS (m/z): 230.0 (M+H). at reflux overnight the mixture is concentrated The residue is partitioned between H2O (50 mL) and EtOAc (50 mL) it is extracted with EtOAc The organic extracts are dried concentrated The residue is purified by silica gel column chromatography eluting with DCM:MeOH (25:1)

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

Procedure: Ethyl malonyl chloride (15.1 g, 0.10 mol) was added to a mixed solution of aniline (9.3 g, 0.10 mol), triethylamine (11.1 g, 0.11 mol), N,N-dimethylaminopyridine (1.5 g, 0.012 mol) and dichloromethane (300 mL), at 10° C. or below. This mixture was stirred for 3 hours at room temperature, and then poured into water. The organic layer was washed with diluted hydrochloric acid, aqueous saturated sodium bicarbonate and saturated brine, in this order. The obtained organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure, to obtain 19.5 g of a subject compound (yield: 94%). The organic layer was washed with diluted hydrochloric acid, aqueous saturated sodium bicarbonate and saturated brine, in this order The obtained organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure