苯甲酸(3-氯丙基)酯

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

实验步骤: To a solution of 1,2-dihydro-4-[(4-iodophenyl)methyl]-5-isopropyl-3H-pyrazol-3-one (5 g) and imidazole (1.19 g) in N,N-dimethylformamide (20 mL) was added triisopropylsilyl chloride (3.1 g) at room temperature, and the mixture was stirred for 3 hours. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 4-[(4-iodophenyl)methyl]-5-isopropyl-3-triisopropylsilyloxy-1H-pyrazole (7.27 g). To a solution of obtained 4-[(4-iodophenyl)methyl]-5-isopropyl-3-triisopropylsilyloxy-1H-pyrazole (3 g) in N,N-dimethylformamide (10 mL) was added sodium hydride (55%, 0.33 g) under ice-cooling, and the mixture was stirred for 20 minutes. To the reaction mixture were added a solution of 1-benzoyloxy-3-chloropropane (3.0 g) in N,N-dimethylformamide (10 mL) and potassium iodide (0.25 g) at the same temperature, and the resulting mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1-10/1) to give 1-(3-benzoyloxypropyl)-4-[(4-iodophenyl)methyl]-5-isopropyl-3-triisopropylsilyloxy-1H-pyrazole (2.55 g). This material was dissolved in tetrahydrofuran (3 mL). To the solution was added 4 mol/L hydrochloric acid (1,4-dioxane solution, 10 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, and the resulting mixture was poured into water. The organic layer was separated, and the organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue was added a mixed solvent of n-hexane and ethyl acetate (20/1) (10 mL), and the mixture was stirred at room temperature for 1 hour. The precipitated crystals were collected by filtration, and washed with a mixed solvent of n-hexane and ethyl acetate (20/1) and dried under reduced pressure to give the title compound (0.85 g). cooling the resulting mixture was stirred at room temperature overnight the mixture was extracted with ethyl acetate The extract was washed with water and brine dried over anhydrous sodium sulfate The solvent was removed under reduced pressure the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1-10/1)

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

实验步骤: To a solution of 1,2-dihydro-4-[(4-iodophenyl)methyl]-5-isopropyl-3H-pyrazol-3-one (5 g) and imidazole (1.19 g) in N,N-dimethylformamide (20 mL) was added triisopropylsilyl chloride (3.1 g) at room temperature, and the mixture was stirred for 3 hours. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 4-[(4-iodophenyl)methyl]-5-isopropyl-3-triisopropylsilyloxy-1H-pyrazole (7.27 g). To a solution of obtained 4-[(4-iodophenyl)methyl]-5-isopropyl-3-triisopropylsilyloxy-1H-pyrazole (3 g) in N,N-dimethylformamide (10 mL) was added sodium hydride (55%, 0.33 g) under ice-cooling, and the mixture was stirred for 20 minutes. To the reaction mixture were added a solution of 1-benzoyloxy-3-chloropropane (3.0 g) in N,N-dimethylformamide (10 mL) and potassium iodide (0.25 g) at the same temperature, and the resulting mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1-10/1) to give 1-(3-benzoyloxypropyl)-4-[(4-iodophenyl)methyl]-5-isopropyl-3-triisopropylsilyloxy-1H-pyrazole (2.55 g). This material was dissolved in tetrahydrofuran (3 mL). To the solution was added 4 mol/L hydrochloric acid (1,4-dioxane solution, 10 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, and the resulting mixture was poured into water. The organic layer was separated, and the organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue was added a mixed solvent of n-hexane and ethyl acetate (20/1) (10 mL), and the mixture was stirred at room temperature for 1 hour. The precipitated crystals were collected by filtration, and washed with a mixed solvent of n-hexane and ethyl acetate (20/1) and dried under reduced pressure to give the title compound (0.85 g). cooling the resulting mixture was stirred at room temperature overnight the mixture was extracted with ethyl acetate The extract was washed with water and brine dried over anhydrous sodium sulfate The solvent was removed under reduced pressure the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1-10/1)

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

实验步骤: To a solution of 1,2-dihydro-4-[(4-iodophenyl)methyl]-5-isopropyl-3H-pyrazol-3-one (5 g) and imidazole (1.19 g) in N,N-dimethylformamide (20 mL) was added triisopropylsilyl chloride (3.1 g) at room temperature, and the mixture was stirred for 3 hours. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 4-[(4-iodophenyl)methyl]-5-isopropyl-3-triisopropylsilyloxy-1H-pyrazole (7.27 g). To a solution of obtained 4-[(4-iodophenyl)methyl]-5-isopropyl-3-triisopropylsilyloxy-1H-pyrazole (3 g) in N,N-dimethylformamide (10 mL) was added sodium hydride (55%, 0.33 g) under ice-cooling, and the mixture was stirred for 20 minutes. To the reaction mixture were added a solution of 1-benzoyloxy-3-chloropropane (3.0 g) in N,N-dimethylformamide (10 mL) and potassium iodide (0.25 g) at the same temperature, and the resulting mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1-10/1) to give 1-(3-benzoyloxypropyl)-4-[(4-iodophenyl)methyl]-5-isopropyl-3-triisopropylsilyloxy-1H-pyrazole (2.55 g). This material was dissolved in tetrahydrofuran (3 mL). To the solution was added 4 mol/L hydrochloric acid (1,4-dioxane solution, 10 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, and the resulting mixture was poured into water. The organic layer was separated, and the organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue was added a mixed solvent of n-hexane and ethyl acetate (20/1) (10 mL), and the mixture was stirred at room temperature for 1 hour. The precipitated crystals were collected by filtration, and washed with a mixed solvent of n-hexane and ethyl acetate (20/1) and dried under reduced pressure to give the title compound (0.85 g). cooling the resulting mixture was stirred at room temperature overnight the mixture was extracted with ethyl acetate The extract was washed with water and brine dried over anhydrous sodium sulfate The solvent was removed under reduced pressure the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1-10/1)

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-chloro-4-methoxyphenol (15.5 gm) in DMF (20 ml) was added to a suspension of 60% sodium hydride (4 gm) in DMF (10 ml). To the resulting solution there was added a solution of 3-chloropropyl benzoate (15.5 gm) in DMF (20 ml). The solution was heated at 80° C. for 20 hrs, then diluted with ethyl acetate, then washed with water then dried and then evaporated. The crude product was dissolved in a 1:1 mixture of methanol/THF (40 ml) to which 10% sodium hydroxide (50 ml) was added. The mixture was refluxed for 3 hrs, then diluted with ethyl acetate, then washed with water and then evaporated. The crude product was purified by chromatography on silica gel using 40% ethyl acetate in hexane as the eluting solvent. The product was then dissolved in dichloroethane (40 ml) containing paraformaldehyde (2.25 gm). The solution was cooled in an ice bath and a stream of HCl gas was bubbled through the solution for 3.5 hrs. The solution was then dried over magnesium sulfate and the solvent was then removed under reduced pressure. Following the procedure set forth in Steps (2) to (4) of Preparation A, the resulting 3-(2-chloro-4-methoxyphenoxy) propyloxymethyl chloride was reacted with isatoic anhydride to give 1-[3-(2-chloro-4-methoxyphenoxy)-propyloxymethyl]-4-hydroxy-2(1H)-quinolinone. That the expected product was obtained was confirmed by the spectral data: MS: m/e 389 (M·+); NMR (DMSO): δ1.9 (t, 2H, CH2), 3.65 (t, 2H, CH2O), 3.70 (s, 3H, OCH3), 3.90 (t, 2H, CH2O), 5.65 (s, 2H, NCH2O), 5.84 (s, 1H, =CH). washed with water then dried evaporated The crude product was dissolved in a 1:1 mixture of methanol/THF (40 ml) to which 10% sodium hydroxide (50 ml) was added The mixture was refluxed for 3 hrs diluted with ethyl acetate washed with water evaporated The crude product was purified by chromatography on silica gel using 40% ethyl acetate in hexane as the eluting solvent The product was then dissolved in dichloroethane (40 ml) containing paraformaldehyde (2.25 gm) The solution was cooled in an ice bath a stream of HCl gas was bubbled through the solution for 3.5 hrs The solution was then dried over magnesium sulfate the solvent was then removed under reduced pressure set forth in Steps (2) to (4) of Preparation A