5'-氯-2'-羟基苯基乙基(甲)酮

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 39.4 g quantity of 4-[(dimethoxyphosphoryl)methyl]benzoyl chloride was dissolved in 150 ml of dry dichloromethane. Then 150 ml of a pyridine solution containing 27.7 g of 5'-chloro-2'-hydroxypropiophenone was slowly added dropwise to the reaction mixture with stirring under ice-cooling, and the stirring was continued at room temperature for 10 hours. After addition of 150 ml of water, the reaction mixture was extracted with chloroform. The chloroform layer was washed serially with 300 ml of a 10% aqueous HCl solution and 200 ml of water and dried over Glauber's salt. The solvent was distilled off under reduced pressure, and the residue thus obtained was dissolved in 150 ml of pyridine. A 14.0 g quantity of potassium hydroxide was added to the solution with stirring at room temperature, and the mixture was heated at 50° C. with stirring for 2 hours. After addition of 300 ml of a 10% aqueous HCl solution, the reaction mixture was extracted with chloroform. The chloroform layer was washed with 100 ml of water and dried over Glauber's salt. The solvent was distilled off under reduced pressure and the residue was subjected to silica gel column chromatography (eluent: chloroform:ethyl acetate=1:1). The resulting crude crystals were recrystallized from dichloromethane-n-hexane to provide 3.9 g of the title compound as colorless crystals. Table 1 shows the structure and physical property of the compound obtained. was slowly added dropwise to the reaction mixture cooling the reaction mixture was extracted with chloroform The chloroform layer was washed serially with 300 ml of a 10% aqueous HCl solution and 200 ml of water dried over Glauber's salt The solvent was distilled off under reduced pressure the residue thus obtained with stirring at room temperature with stirring for 2 hours the reaction mixture was extracted with chloroform The chloroform layer was washed with 100 ml of water dried over Glauber's salt The solvent was distilled off under reduced pressure The resulting crude crystals were recrystallized from dichloromethane-n-hexane

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 39.4 g quantity of 4-[(dimethoxyphosphoryl)methyl]benzoyl chloride was dissolved in 150 ml of dry dichloromethane. Then 150 ml of a pyridine solution containing 27.7 g of 5'-chloro-2'-hydroxypropiophenone was slowly added dropwise to the reaction mixture with stirring under ice-cooling, and the stirring was continued at room temperature for 10 hours. After addition of 150 ml of water, the reaction mixture was extracted with chloroform. The chloroform layer was washed serially with 300 ml of a 10% aqueous HCl solution and 200 ml of water and dried over Glauber's salt. The solvent was distilled off under reduced pressure, and the residue thus obtained was dissolved in 150 ml of pyridine. A 14.0 g quantity of potassium hydroxide was added to the solution with stirring at room temperature, and the mixture was heated at 50° C. with stirring for 2 hours. After addition of 300 ml of a 10% aqueous HCl solution, the reaction mixture was extracted with chloroform. The chloroform layer was washed with 100 ml of water and dried over Glauber's salt. The solvent was distilled off under reduced pressure and the residue was subjected to silica gel column chromatography (eluent: chloroform:ethyl acetate=1:1). The resulting crude crystals were recrystallized from dichloromethane-n-hexane to provide 3.9 g of the title compound as colorless crystals. Table 1 shows the structure and physical property of the compound obtained. was slowly added dropwise to the reaction mixture cooling the reaction mixture was extracted with chloroform The chloroform layer was washed serially with 300 ml of a 10% aqueous HCl solution and 200 ml of water dried over Glauber's salt The solvent was distilled off under reduced pressure the residue thus obtained with stirring at room temperature with stirring for 2 hours the reaction mixture was extracted with chloroform The chloroform layer was washed with 100 ml of water dried over Glauber's salt The solvent was distilled off under reduced pressure The resulting crude crystals were recrystallized from dichloromethane-n-hexane

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3-(Morpholinosulfonyl)benzohydrazide (40 mg, 0.140 mmol) and 1-(5-chloro-2-hydroxyphenyl)propan-1-one (25.9 mg, 0.140 mmol) were dissolved in methanol (4 mL) in the presence of acetic acid as a catalyst, and the reaction mixture was heated via microwave irradiation to 120° C. for 30 min. The reaction was monitored by TLC. Upon completion of the reaction and following cooling, the solvent was removed by vacuum, and the resulting crude material was purified by flash column chromatography (2% CH3OH/CH2Cl2) affording the title compound as a solid (20 mg). 1H NMR (400 MHz, acetone-d6): δ 8.26 (m, 2H), 8.00 (d, 1H, J=7.6 Hz), 7.84 (t, 1H, J=8.0 Hz), 7.64 (d, 1H, J=2.4 Hz), 7.33 (m, 1H), 6.98 (d, 1H, J=9.2 Hz), 3.69 (m, 4H), 3.10 (q, 2H, J=7.6 Hz), 2.99 (m, 4H), 1.26 (t, 3H, J=7.6 Hz). ESI-MS: 452.1 [M+H]+. Upon completion of the reaction following cooling the solvent was removed by vacuum the resulting crude material was purified by flash column chromatography (2% CH3OH/CH2Cl2)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diethylcarbonate (27.2 mmol, 3.3 mL) is dissolved in 30 mL toluene, and NaH (16.3 mmol, 0.65 g of 60% dispersion) is added in portions. 5′-chloro-2′-hydroxy-propiophenone (5.4 mmol, 1.0 g) in 10 mL is dissolved in toluene and is added dropwise via an addition funnel to the above solution. The cloudy yellow-green mixture is heated to near reflux for 20 hrs then is cooled to ambient temperature. 1N NaOH (50 mL) is added and the mixture stirred at ambient temperature for 60 hrs. The layers are separated and the organic layer is washed with H2O. The combined aqueous layers are washed with Et2O and the aqueous layer then acidified to pH 2 with conc. HCl. The resulting off-white precipitate is filtered, is washed with Et2O, and is dried to afford the title compound (0.417 g, 37%). A second crop is obtained by refrigerating the filtrate (0.442 g, 39%). 1H NMR (DMSO-d6, 300 MHz) δ 11.50 (1H, br s), 7.88 (1H, d, J=2.5 Hz), 7.61 (1H, dd, J=2.62, 8.87 Hz), 7.40 (1H, d, J=8.87 Hz), 2.00 (3H, s); MS (ESI, Pos.) calcd for C10H7ClO3 ml/z [M+H]=211.0, found 210.9. is added dropwise via an addition funnel to the above solution The cloudy yellow-green mixture is heated to near reflux for 20 hrs The layers are separated the organic layer is washed with H2O The combined aqueous layers are washed with Et2O The resulting off-white precipitate is filtered is washed with Et2O is dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diethylcarbonate (27.2 mmol, 3.3 mL) is dissolved in 30 mL toluene, and NaH (16.3 mmol, 0.65 g of 60% dispersion) is added in portions. 5′-chloro-2′-hydroxy-propiophenone (5.4 mmol, 1.0 g) in 10 mL is dissolved in toluene and is added dropwise via an addition funnel to the above solution. The cloudy yellow-green mixture is heated to near reflux for 20 hrs then is cooled to ambient temperature. 1N NaOH (50 mL) is added and the mixture stirred at ambient temperature for 60 hrs. The layers are separated and the organic layer is washed with H2O. The combined aqueous layers are washed with Et2O and the aqueous layer then acidified to pH 2 with conc. HCl. The resulting off-white precipitate is filtered, is washed with Et2O, and is dried to afford the title compound (0.417 g, 37%). A second crop is obtained by refrigerating the filtrate (0.442 g, 39%). 1H NMR (DMSO-d6, 300 MHz) δ 11.50 (1H, br s), 7.88 (1H, d, J=2.5 Hz), 7.61 (1H, dd, J=2.62, 8.87 Hz), 7.40 (1H, d, J=8.87 Hz), 2.00 (3H, s); MS (ESI, Pos.) calcd for C10H7ClO3 ml/z [M+H]=211.0, found 210.9. is added dropwise via an addition funnel to the above solution The cloudy yellow-green mixture is heated to near reflux for 20 hrs The layers are separated the organic layer is washed with H2O The combined aqueous layers are washed with Et2O The resulting off-white precipitate is filtered is washed with Et2O is dried

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 39.4 g quantity of 4-[(dimethoxyphosphoryl)methyl]benzoyl chloride was dissolved in 150 ml of dry dichloromethane. Then 150 ml of a pyridine solution containing 27.7 g of 5'-chloro-2'-hydroxypropiophenone was slowly added dropwise to the reaction mixture with stirring under ice-cooling, and the stirring was continued at room temperature for 10 hours. After addition of 150 ml of water, the reaction mixture was extracted with chloroform. The chloroform layer was washed serially with 300 ml of a 10% aqueous HCl solution and 200 ml of water and dried over Glauber's salt. The solvent was distilled off under reduced pressure, and the residue thus obtained was dissolved in 150 ml of pyridine. A 14.0 g quantity of potassium hydroxide was added to the solution with stirring at room temperature, and the mixture was heated at 50° C. with stirring for 2 hours. After addition of 300 ml of a 10% aqueous HCl solution, the reaction mixture was extracted with chloroform. The chloroform layer was washed with 100 ml of water and dried over Glauber's salt. The solvent was distilled off under reduced pressure and the residue was subjected to silica gel column chromatography (eluent: chloroform:ethyl acetate=1:1). The resulting crude crystals were recrystallized from dichloromethane-n-hexane to provide 3.9 g of the title compound as colorless crystals. Table 1 shows the structure and physical property of the compound obtained. was slowly added dropwise to the reaction mixture cooling the reaction mixture was extracted with chloroform The chloroform layer was washed serially with 300 ml of a 10% aqueous HCl solution and 200 ml of water dried over Glauber's salt The solvent was distilled off under reduced pressure the residue thus obtained with stirring at room temperature with stirring for 2 hours the reaction mixture was extracted with chloroform The chloroform layer was washed with 100 ml of water dried over Glauber's salt The solvent was distilled off under reduced pressure The resulting crude crystals were recrystallized from dichloromethane-n-hexane

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3-(Morpholinosulfonyl)benzohydrazide (40 mg, 0.140 mmol) and 1-(5-chloro-2-hydroxyphenyl)propan-1-one (25.9 mg, 0.140 mmol) were dissolved in methanol (4 mL) in the presence of acetic acid as a catalyst, and the reaction mixture was heated via microwave irradiation to 120° C. for 30 min. The reaction was monitored by TLC. Upon completion of the reaction and following cooling, the solvent was removed by vacuum, and the resulting crude material was purified by flash column chromatography (2% CH3OH/CH2Cl2) affording the title compound as a solid (20 mg). 1H NMR (400 MHz, acetone-d6): δ 8.26 (m, 2H), 8.00 (d, 1H, J=7.6 Hz), 7.84 (t, 1H, J=8.0 Hz), 7.64 (d, 1H, J=2.4 Hz), 7.33 (m, 1H), 6.98 (d, 1H, J=9.2 Hz), 3.69 (m, 4H), 3.10 (q, 2H, J=7.6 Hz), 2.99 (m, 4H), 1.26 (t, 3H, J=7.6 Hz). ESI-MS: 452.1 [M+H]+. Upon completion of the reaction following cooling the solvent was removed by vacuum the resulting crude material was purified by flash column chromatography (2% CH3OH/CH2Cl2)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diethylcarbonate (27.2 mmol, 3.3 mL) is dissolved in 30 mL toluene, and NaH (16.3 mmol, 0.65 g of 60% dispersion) is added in portions. 5′-chloro-2′-hydroxy-propiophenone (5.4 mmol, 1.0 g) in 10 mL is dissolved in toluene and is added dropwise via an addition funnel to the above solution. The cloudy yellow-green mixture is heated to near reflux for 20 hrs then is cooled to ambient temperature. 1N NaOH (50 mL) is added and the mixture stirred at ambient temperature for 60 hrs. The layers are separated and the organic layer is washed with H2O. The combined aqueous layers are washed with Et2O and the aqueous layer then acidified to pH 2 with conc. HCl. The resulting off-white precipitate is filtered, is washed with Et2O, and is dried to afford the title compound (0.417 g, 37%). A second crop is obtained by refrigerating the filtrate (0.442 g, 39%). 1H NMR (DMSO-d6, 300 MHz) δ 11.50 (1H, br s), 7.88 (1H, d, J=2.5 Hz), 7.61 (1H, dd, J=2.62, 8.87 Hz), 7.40 (1H, d, J=8.87 Hz), 2.00 (3H, s); MS (ESI, Pos.) calcd for C10H7ClO3 ml/z [M+H]=211.0, found 210.9. is added dropwise via an addition funnel to the above solution The cloudy yellow-green mixture is heated to near reflux for 20 hrs The layers are separated the organic layer is washed with H2O The combined aqueous layers are washed with Et2O The resulting off-white precipitate is filtered is washed with Et2O is dried

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 39.4 g quantity of 4-[(dimethoxyphosphoryl)methyl]benzoyl chloride was dissolved in 150 ml of dry dichloromethane. Then 150 ml of a pyridine solution containing 27.7 g of 5'-chloro-2'-hydroxypropiophenone was slowly added dropwise to the reaction mixture with stirring under ice-cooling, and the stirring was continued at room temperature for 10 hours. After addition of 150 ml of water, the reaction mixture was extracted with chloroform. The chloroform layer was washed serially with 300 ml of a 10% aqueous HCl solution and 200 ml of water and dried over Glauber's salt. The solvent was distilled off under reduced pressure, and the residue thus obtained was dissolved in 150 ml of pyridine. A 14.0 g quantity of potassium hydroxide was added to the solution with stirring at room temperature, and the mixture was heated at 50° C. with stirring for 2 hours. After addition of 300 ml of a 10% aqueous HCl solution, the reaction mixture was extracted with chloroform. The chloroform layer was washed with 100 ml of water and dried over Glauber's salt. The solvent was distilled off under reduced pressure and the residue was subjected to silica gel column chromatography (eluent: chloroform:ethyl acetate=1:1). The resulting crude crystals were recrystallized from dichloromethane-n-hexane to provide 3.9 g of the title compound as colorless crystals. Table 1 shows the structure and physical property of the compound obtained. was slowly added dropwise to the reaction mixture cooling the reaction mixture was extracted with chloroform The chloroform layer was washed serially with 300 ml of a 10% aqueous HCl solution and 200 ml of water dried over Glauber's salt The solvent was distilled off under reduced pressure the residue thus obtained with stirring at room temperature with stirring for 2 hours the reaction mixture was extracted with chloroform The chloroform layer was washed with 100 ml of water dried over Glauber's salt The solvent was distilled off under reduced pressure The resulting crude crystals were recrystallized from dichloromethane-n-hexane