ethyl 3-anilinopropanoate

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: According to the procedure of P. L. Southwick, J. Am. Chem. Soc. 75 3413 (1953), to a solution of aniline (31.86 g, 0.35 mol) and ethyl acrylate (35.0 g, 0.35 mol) in 200 ml of dry benzene (freshly distilled from CaH2) was added 0.5 ml of tin tetrachloride and the resulting solution was heated under reflux for 24 h. After cooling to room temperature the suspension was filtered to remove the inorganic solids and then concentrated in vacuo to give a dark green oil which was chromatographed on silica gel eluting with ethyl acetate/toluene (30/70) to give the title compound (40.7 g, 60%) as a light yellow oil. B.p. 95°-98° C. at 0.1 mm Hg. the resulting solution was heated under reflux for 24 h was filtered to remove the inorganic solids concentrated in vacuo to give a dark green oil which was chromatographed on silica gel eluting with ethyl acetate/toluene (30/70)

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

実験手順: According to the procedure of P. L. Southwick, J. Am. Chem. Soc. 75 3413 (1953), to a solution of aniline (31.86 g, 0.35 mol) and ethyl acrylate (35.0 g, 0.35 mol) in 200 ml of dry benzene (freshly distilled from CaH2) was added 0.5 ml of tin tetrachloride and the resulting solution was heated under reflux for 24 h. After cooling to room temperature the suspension was filtered to remove the inorganic solids and then concentrated in vacuo to give a dark green oil which was chromatographed on silica gel eluting with ethyl acetate/toluene (30/70) to give the title compound (40.7 g, 60%) as a light yellow oil. B.p. 95°-98° C. at 0.1 mm Hg. the resulting solution was heated under reflux for 24 h was filtered to remove the inorganic solids concentrated in vacuo to give a dark green oil which was chromatographed on silica gel eluting with ethyl acetate/toluene (30/70)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Phenyl-β-alanine ethyl ester (24,25 g) is dissolved in benzene (60 ml), and thereto is added dropwise diketene (12 ml) at 70° C. The mixture is refluxed overnight. The mixture is distilled to remove the solvent to give crude N-phenyl-N-methoxycarbonylmethylcarbonyl-β-alanine ethyl ester (37.23 g). Said crude compound is dissolved in methanol (70 ml), and the mixture is added dropwise to a solution of sodium methoxide (prepared from 3.90 g of sodium) in methanol (70 ml) at 50° C. The mixture is stirred at 50° C. for 2 hours, and distilled to remove the solvent. The residue is dissolved in water, and the aqueous solution is extracted with ethyl acetate. The aqueous layer is neutralized with 10% HCl, and extracted with ethyl acetate. The extract is washed with a saturated sodium chloride solution, dried and then distilled to remove the solvent. The residue is purified by silica gel column chromatography (solvent, ethyl acetate:n-hexane=1:2) to give 1-phenyl-3-acetyl-2,4-dioxopiperidine (23.87 g, 81.6%) as oil. The mixture is refluxed overnight The mixture is distilled to remove the solvent to give crude N-phenyl-N-methoxycarbonylmethylcarbonyl-β-alanine ethyl ester (37.23 g) distilled to remove the solvent The residue is dissolved in water the aqueous solution is extracted with ethyl acetate extracted with ethyl acetate The extract is washed with a saturated sodium chloride solution dried distilled to remove the solvent The residue is purified by silica gel column chromatography (solvent, ethyl acetate:n-hexane=1:2)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Phenyl-β-alanine ethyl ester (24,25 g) is dissolved in benzene (60 ml), and thereto is added dropwise diketene (12 ml) at 70° C. The mixture is refluxed overnight. The mixture is distilled to remove the solvent to give crude N-phenyl-N-methoxycarbonylmethylcarbonyl-β-alanine ethyl ester (37.23 g). Said crude compound is dissolved in methanol (70 ml), and the mixture is added dropwise to a solution of sodium methoxide (prepared from 3.90 g of sodium) in methanol (70 ml) at 50° C. The mixture is stirred at 50° C. for 2 hours, and distilled to remove the solvent. The residue is dissolved in water, and the aqueous solution is extracted with ethyl acetate. The aqueous layer is neutralized with 10% HCl, and extracted with ethyl acetate. The extract is washed with a saturated sodium chloride solution, dried and then distilled to remove the solvent. The residue is purified by silica gel column chromatography (solvent, ethyl acetate:n-hexane=1:2) to give 1-phenyl-3-acetyl-2,4-dioxopiperidine (23.87 g, 81.6%) as oil. The mixture is refluxed overnight The mixture is distilled to remove the solvent to give crude N-phenyl-N-methoxycarbonylmethylcarbonyl-β-alanine ethyl ester (37.23 g) distilled to remove the solvent The residue is dissolved in water the aqueous solution is extracted with ethyl acetate extracted with ethyl acetate The extract is washed with a saturated sodium chloride solution dried distilled to remove the solvent The residue is purified by silica gel column chromatography (solvent, ethyl acetate:n-hexane=1:2)

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

実験手順: 1.4 g (4.6 mmol) of 3-methyl-2-[2-(4-cyanophenyl)ethyl]imidazo[1,2-a]pyridin-7-yl-carboxylic acid (prepared from 4-bromo-l-(4-cyanophenyl)-1-penten-3-one and methyl 2-aminopyridine-4-carboxylate analogously to Y. Katsura et al., Chem. Pharm. Bull. 1992, 40, 1424-1438) were suspended in 15 mL of thionyl chloride and heated to boiling for 1 hour until fully dissolved. After the thionyl chloride had been distilled off, the acid chloride was dissolved in 15 mL of pyridine without any further purification and at 0° C. mixed with 1.0 g (5.2 mmol) of N-(2-ethoxycarbonylethyl)aniline. After 1 hour, the solvent was distilled off, the residue was taken up in 30 mL of methylene chloride, washed with 15 mL of 1N hydrochloric acid, and dried with sodium sulfate. After distillation of the solvent and chromatography (silica gel; methylene chloride/ethanol=0 to 2%), a brown oil was obtained. Yield: 1.48 g (64% of theory); Rf value: 0.73 (silica gel; ethyl acetate/ethanol/ammonia=90:10:1). heated until fully dissolved After the thionyl chloride had been distilled off the acid chloride was dissolved in 15 mL of pyridine without any further purification and at 0° C. After 1 hour the solvent was distilled off washed with 15 mL of 1N hydrochloric acid dried with sodium sulfate After distillation of the solvent and chromatography (silica gel; methylene chloride/ethanol=0 to 2%) a brown oil was obtained

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

実験手順: To a solution of 24.7 g (0.115 mol) of 4-methylamino-3-nitrobenzoic acid chloride and 22.3 g (0.115 mol) of N-(2-ethoxycarbonylethyl)aniline in 300 mL of tetrahydrofuran, 13.1 g (0.13 mol) of triethylamine were added dropwise in 15 minutes, with stirring, at room temperature. After 2 hours stirring, the solvent was distilled off in a water-jet vacuum and the residue was mixed with 700 mL of water with stirring. The mixture was extracted 3 times with 200 mL of dichloromethane, the organic extract was washed twice with 200 mL of 2N hydrochloric acid and twice with 300 mL of water and dried over sodium sulfate. The solvent was then distilled off and the oily product thus obtained was purified by column chromatography (1 kg silica gel; eluant: petroleum ether/ethyl acetate=2:1). Yield: 35.0 g (82% of theory); Rf value: 0.28 (silica gel; dichloromethane/ethanol=50:1). After 2 hours stirring the solvent was distilled off in a water-jet vacuum the residue was mixed with 700 mL of water with stirring The mixture was extracted 3 times with 200 mL of dichloromethane the organic extract was washed twice with 200 mL of 2N hydrochloric acid and twice with 300 mL of water dried over sodium sulfate The solvent was then distilled off the oily product thus obtained was purified by column chromatography (1 kg silica gel; eluant: petroleum ether/ethyl acetate=2:1)

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

実験手順: A suspension of 1.6 g (7.2 mmol) of 2-methoxymethylbenzothiazole-5-carboxylic acid in 60 mL dichloromethane was mixed with 1.6 mL (22 mmol) of thionyl chloride and refluxed for 1 hour. The solid dissolved after 20 minutes. After distillation of the liquid components, the crude product was taken up in dichloromethane twice more and each time the solvent was distilled off. The crude acid chloride thus obtained was taken up in 50 mL of tetrahydrofuran, added dropwise to a mixture of 1.4 g (7.2 mmol) of N-(2-ethoxycarbonylethyl)aniline and 3.0 mL (21 mmol) of triethylamine in 50 mL of tetrahydrofuran and stirred overnight at room temperature. Then the solvent was distilled off in vacuo, the residue was taken up in 30 mL of dichloromethane, this solution was washed with water, and dried with sodium sulfate. After distillation of the solvent and flash chromatography (silica gel; gradient: dichloromethane/ethanol 98.5:1.5 to 80:20), the desired compound was isolated as a brownish oil. Yield: 2.05 (72% of theory); Rf value: 0.40 (silica gel; ethyl acetate/petroleum ether=1:1). refluxed for 1 hour The solid dissolved after 20 minutes After distillation of the liquid components each time the solvent was distilled off The crude acid chloride thus obtained Then the solvent was distilled off in vacuo this solution was washed with water dried with sodium sulfate After distillation of the solvent and flash chromatography (silica gel; gradient: dichloromethane/ethanol 98.5:1.5 to 80:20)

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

実験手順: 1.4 g (4.6 mmol) of 3-methyl-2-[2-(4-cyanophenyl)ethyl]imidazo[1,2-a]pyridin-7-yl-carboxylic acid (prepared from 4-bromo-l-(4-cyanophenyl)-1-penten-3-one and methyl 2-aminopyridine-4-carboxylate analogously to Y. Katsura et al., Chem. Pharm. Bull. 1992, 40, 1424-1438) were suspended in 15 mL of thionyl chloride and heated to boiling for 1 hour until fully dissolved. After the thionyl chloride had been distilled off, the acid chloride was dissolved in 15 mL of pyridine without any further purification and at 0° C. mixed with 1.0 g (5.2 mmol) of N-(2-ethoxycarbonylethyl)aniline. After 1 hour, the solvent was distilled off, the residue was taken up in 30 mL of methylene chloride, washed with 15 mL of 1N hydrochloric acid, and dried with sodium sulfate. After distillation of the solvent and chromatography (silica gel; methylene chloride/ethanol=0 to 2%), a brown oil was obtained. Yield: 1.48 g (64% of theory); Rf value: 0.73 (silica gel; ethyl acetate/ethanol/ammonia=90:10:1). heated until fully dissolved After the thionyl chloride had been distilled off the acid chloride was dissolved in 15 mL of pyridine without any further purification and at 0° C. After 1 hour the solvent was distilled off washed with 15 mL of 1N hydrochloric acid dried with sodium sulfate After distillation of the solvent and chromatography (silica gel; methylene chloride/ethanol=0 to 2%) a brown oil was obtained

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

実験手順: To a solution of 24.7 g (0.115 mol) of 4-methylamino-3-nitrobenzoic acid chloride and 22.3 g (0.115 mol) of N-(2-ethoxycarbonylethyl)aniline in 300 mL of tetrahydrofuran, 13.1 g (0.13 mol) of triethylamine were added dropwise in 15 minutes, with stirring, at room temperature. After 2 hours stirring, the solvent was distilled off in a water-jet vacuum and the residue was mixed with 700 mL of water with stirring. The mixture was extracted 3 times with 200 mL of dichloromethane, the organic extract was washed twice with 200 mL of 2N hydrochloric acid and twice with 300 mL of water and dried over sodium sulfate. The solvent was then distilled off and the oily product thus obtained was purified by column chromatography (1 kg silica gel; eluant: petroleum ether/ethyl acetate=2:1). Yield: 35.0 g (82% of theory); Rf value: 0.28 (silica gel; dichloromethane/ethanol=50:1). After 2 hours stirring the solvent was distilled off in a water-jet vacuum the residue was mixed with 700 mL of water with stirring The mixture was extracted 3 times with 200 mL of dichloromethane the organic extract was washed twice with 200 mL of 2N hydrochloric acid and twice with 300 mL of water dried over sodium sulfate The solvent was then distilled off the oily product thus obtained was purified by column chromatography (1 kg silica gel; eluant: petroleum ether/ethyl acetate=2:1)

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

実験手順: A suspension of 1.6 g (7.2 mmol) of 2-methoxymethylbenzothiazole-5-carboxylic acid in 60 mL dichloromethane was mixed with 1.6 mL (22 mmol) of thionyl chloride and refluxed for 1 hour. The solid dissolved after 20 minutes. After distillation of the liquid components, the crude product was taken up in dichloromethane twice more and each time the solvent was distilled off. The crude acid chloride thus obtained was taken up in 50 mL of tetrahydrofuran, added dropwise to a mixture of 1.4 g (7.2 mmol) of N-(2-ethoxycarbonylethyl)aniline and 3.0 mL (21 mmol) of triethylamine in 50 mL of tetrahydrofuran and stirred overnight at room temperature. Then the solvent was distilled off in vacuo, the residue was taken up in 30 mL of dichloromethane, this solution was washed with water, and dried with sodium sulfate. After distillation of the solvent and flash chromatography (silica gel; gradient: dichloromethane/ethanol 98.5:1.5 to 80:20), the desired compound was isolated as a brownish oil. Yield: 2.05 (72% of theory); Rf value: 0.40 (silica gel; ethyl acetate/petroleum ether=1:1). refluxed for 1 hour The solid dissolved after 20 minutes After distillation of the liquid components each time the solvent was distilled off The crude acid chloride thus obtained Then the solvent was distilled off in vacuo this solution was washed with water dried with sodium sulfate After distillation of the solvent and flash chromatography (silica gel; gradient: dichloromethane/ethanol 98.5:1.5 to 80:20)

反応条件: temp:0.00; pressure:0.00; stir: