ethyl 2-(4-chlorophenyl)-3-oxopropanoate

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

実験手順: Then, 14.2 g of ethyl p-chlorophenyl-(α-formyl)acetate and 6.5 g of urethane were added to 50 ml of toluene containing 0.3 ml of concentrated sulfuric acid, and the mixture was heated at reflux while distilling out water which was formed during the reaction until no further water was distilled out. Thereafter, the solvent was distilled off, and the residue was extracted with diethyl ether while hot. The solvent was distilled off from the extract to obtain 13.7 g of ethyl p-chlorophenyl-(α-ethoxycarbonylaminomethylene)acetate having a melting point of 72° C. the mixture was heated at reflux while distilling out water which was formed during the reaction until no further water was distilled out Thereafter, the solvent was distilled off the residue was extracted with diethyl ether while hot The solvent was distilled off from the extract

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

実験手順: Then, 14.2 g of ethyl p-chlorophenyl-(α-formyl)acetate and 6.5 g of urethane were added to 50 ml of toluene containing 0.3 ml of concentrated sulfuric acid, and the mixture was heated at reflux while distilling out water which was formed during the reaction until no further water was distilled out. Thereafter, the solvent was distilled off, and the residue was extracted with diethyl ether while hot. The solvent was distilled off from the extract to obtain 13.7 g of ethyl p-chlorophenyl-(α-ethoxycarbonylaminomethylene)acetate having a melting point of 72° C. the mixture was heated at reflux while distilling out water which was formed during the reaction until no further water was distilled out Thereafter, the solvent was distilled off the residue was extracted with diethyl ether while hot The solvent was distilled off from the extract

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

実験手順: Then, 4.19 g of sodium hydride (60% in oil) was suspended in 150 ml of tetrahydrofuran, to which a solution of 19.0 g of ethyl 4-chlorophenylacetate in 150 ml of tetrahydrofuran was added dropwise at 5° to 10° C. After stirring at room temperature for 1.5 hours, 8.42 g of ethyl formate was added, and the mixture was further stirred at room temperature for 4.5 hours. After completion of the reaction, the reaction mixture was cooled to ice temperature, neutralized by the addition of diluted hydrochloric acid, and concentrated. The residue was subjected to phase separation with ethyl acetatewater, and the organic layer was dried and then concentrated. The residue was subjected to silica gel chromatography, which afforded 17.0 g of ethyl 2-(4′-chlorophenyl)-2-formylacetate. was added dropwise at 5° to 10° C the mixture was further stirred at room temperature for 4.5 hours After completion of the reaction the reaction mixture was cooled to ice temperature concentrated The residue was subjected to phase separation with ethyl acetatewater the organic layer was dried concentrated

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

実験手順: 2-Amino-3-hydroxypyridine (5.51 g, 0.05 mol) and 2-(4-chlorophenyl)-3-oxo-propanoic acid ethyl ester (13.6 g, 0.06 mol) in EtOH (100 mL) were heated under reflux for 15 h and then allowed to cool. The precipitate was isolated via filtration to yield a 9:1 mixture of the enamine and the cyclized product (11.1 g). under reflux for 15 h to cool The precipitate was isolated via filtration to yield

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

実験手順: 2-Amino-3-hydroxypyridine (5.51 g, 0.05 mol) and 2-(4-chlorophenyl)-3-oxo-propanoic acid ethyl ester (13.6 g, 0.06 mol) in EtOH (100 mL) were heated under reflux for 15 h and then allowed to cool. The precipitate was isolated via filtration to yield a 9:1 mixture of the enamine and the cyclized product (11.1 g). under reflux for 15 h to cool The precipitate was isolated via filtration to yield

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

実験手順: Ethyl formate (7.46 g, 0.101 mol) was added dropwise to a stirred ice-cooled suspension of (4-chlorophenyl)acetic acid ethyl ester (20.0 g, 0.101 mol) and NaH (0.131 mol) in diethyl ether (100 mL). The mixture was then allowed to warm to room temperature overnight. The mixture neutralised (1 M HCl); the organic layer was isolated, dried, and the solvent removed to give 2-(4-chlorophenyl)-3-oxo-propanoic acid ethyl ester as a colourless solid (19.8 g, 87%). 1H NMR (CDCl3): δ 12.14 (d, J=12.8, 1H), 7.31-7.18 (m, 4H), 4.29 (q, J=7.2, 2H), 1.57 (br, 1H), 1.29 (t, J=7.2, 3H). cooled the organic layer was isolated dried the solvent removed

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

実験手順: Then, 4.19 g of sodium hydride (60% in oil) was suspended in 150 ml of tetrahydrofuran, to which a solution of 19.0 g of ethyl 4-chlorophenylacetate in 150 ml of tetrahydrofuran was added dropwise at 5° to 10° C. After stirring at room temperature for 1.5 hours, 8.42 g of ethyl formate was added, and the mixture was further stirred at room temperature for 4.5 hours. After completion of the reaction, the reaction mixture was cooled to ice temperature, neutralized by the addition of diluted hydrochloric acid, and concentrated. The residue was subjected to phase separation with ethyl acetate-water, and the organic layer was dried and then concentrated. The residue was subjected to silica gel chromatography, which afforded 17.0 g of ethyl 2-(4'-chlorophenyl)-2-formylacetate. was added dropwise at 5° to 10° C the mixture was further stirred at room temperature for 4.5 hours After completion of the reaction the reaction mixture was cooled to ice temperature concentrated The residue was subjected to phase separation with ethyl acetate-water the organic layer was dried concentrated

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

実験手順: Then, 14.2 g of ethyl p-chlorophenyl-(α-formyl)acetate and 6.5 g of urethane were added to 50 ml of toluene containing 0.3 ml of concentrated sulfuric acid, and the mixture was heated at reflux while distilling out water which was formed during the reaction until no further water was distilled out. Thereafter, the solvent was distilled off, and the residue was extracted with diethyl ether while hot. The solvent was distilled off from the extract to obtain 13.7 g of ethyl p-chlorophenyl-(α-ethoxycarbonylaminomethylene)acetate having a melting point of 72° C. the mixture was heated at reflux while distilling out water which was formed during the reaction until no further water was distilled out Thereafter, the solvent was distilled off the residue was extracted with diethyl ether while hot The solvent was distilled off from the extract

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

実験手順: Then, 4.19 g of sodium hydride (60% in oil) was suspended in 150 ml of tetrahydrofuran, to which a solution of 19.0 g of ethyl 4-chlorophenylacetate in 150 ml of tetrahydrofuran was added dropwise at 5° to 10° C. After stirring at room temperature for 1.5 hours, 8.42 g of ethyl formate was added, and the mixture was further stirred at room temperature for 4.5 hours. After completion of the reaction, the reaction mixture was cooled to ice temperature, neutralized by the addition of diluted hydrochloric acid, and concentrated. The residue was subjected to phase separation with ethyl acetatewater, and the organic layer was dried and then concentrated. The residue was subjected to silica gel chromatography, which afforded 17.0 g of ethyl 2-(4′-chlorophenyl)-2-formylacetate. was added dropwise at 5° to 10° C the mixture was further stirred at room temperature for 4.5 hours After completion of the reaction the reaction mixture was cooled to ice temperature concentrated The residue was subjected to phase separation with ethyl acetatewater the organic layer was dried concentrated

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

実験手順: 2-Amino-3-hydroxypyridine (5.51 g, 0.05 mol) and 2-(4-chlorophenyl)-3-oxo-propanoic acid ethyl ester (13.6 g, 0.06 mol) in EtOH (100 mL) were heated under reflux for 15 h and then allowed to cool. The precipitate was isolated via filtration to yield a 9:1 mixture of the enamine and the cyclized product (11.1 g). under reflux for 15 h to cool The precipitate was isolated via filtration to yield

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

実験手順: Ethyl formate (7.46 g, 0.101 mol) was added dropwise to a stirred ice-cooled suspension of (4-chlorophenyl)acetic acid ethyl ester (20.0 g, 0.101 mol) and NaH (0.131 mol) in diethyl ether (100 mL). The mixture was then allowed to warm to room temperature overnight. The mixture neutralised (1 M HCl); the organic layer was isolated, dried, and the solvent removed to give 2-(4-chlorophenyl)-3-oxo-propanoic acid ethyl ester as a colourless solid (19.8 g, 87%). 1H NMR (CDCl3): δ 12.14 (d, J=12.8, 1H), 7.31-7.18 (m, 4H), 4.29 (q, J=7.2, 2H), 1.57 (br, 1H), 1.29 (t, J=7.2, 3H). cooled the organic layer was isolated dried the solvent removed