苯并呋喃-2-羧酸甲酯

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

实验步骤: To a solution of 2-benzofuranoic acid methyl ester in carbon disulphide (240 ml) cooled to 5° C. was added acetyl chloride (70 ml) followed portionwise over 1 hour by aluminium trichloride (40 g). The mixture was heated under reflux for 42 hours before cooling and decanting the carbon disulphide. The residual complex was destroyed by the addition of iced water (50 ml) and 2N HCl (50 ml). The resulting mixture was extracted with ethyl acetate (3×200 ml). The organic layers were combined, washed with water (100 ml), dried (MgSO4) and concentrated. The residue was purified by flash column chromatography, eluting with ethyl acetate / hexane (10:90 to 40:60, v/v), to give methyl 5-acetylbenzofuran-2-carboxylate as a solid (3.099 g); NMR 2.68 (3H,s), 4.00(3H,s), 7.6-8.35(4H,m). The mixture was heated under reflux for 42 hours before cooling decanting the carbon disulphide The residual complex was destroyed by the addition of iced water (50 ml) and 2N HCl (50 ml) The resulting mixture was extracted with ethyl acetate (3×200 ml) washed with water (100 ml) dried (MgSO4) concentrated The residue was purified by flash column chromatography eluting with ethyl acetate / hexane (10:90 to 40:60

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

实验步骤: To a solution of 2-benzofuranoic acid methyl ester in carbon disulphide (240 ml) cooled to 5° C. was added acetyl chloride (70 ml) followed portionwise over 1 hour by aluminium trichloride (40 g). The mixture was heated under reflux for 42 hours before cooling and decanting the carbon disulphide. The residual complex was destroyed by the addition of iced water (50 ml) and 2N HCl (50 ml). The resulting mixture was extracted with ethyl acetate (3×200 ml). The organic layers were combined, washed with water (100 ml), dried (MgSO4) and concentrated. The residue was purified by flash column chromatography, eluting with ethyl acetate / hexane (10:90 to 40:60, v/v), to give methyl 5-acetylbenzofuran-2-carboxylate as a solid (3.099 g); NMR 2.68 (3H,s), 4.00(3H,s), 7.6-8.35(4H,m). The mixture was heated under reflux for 42 hours before cooling decanting the carbon disulphide The residual complex was destroyed by the addition of iced water (50 ml) and 2N HCl (50 ml) The resulting mixture was extracted with ethyl acetate (3×200 ml) washed with water (100 ml) dried (MgSO4) concentrated The residue was purified by flash column chromatography eluting with ethyl acetate / hexane (10:90 to 40:60

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The crude product 3 (324 g) was dissolved in anhydrous ethyl ether. The solution was kept under inert atmosphere (nitrogen or argon) and cooled to 0° C. in an ice bath. A 1M solution of lithium aluminum hydride in ether (620 ml) was added dropwise, while stirring, over a period of 1 hour. The solution was then washed with 2N HCl (4×1,000 ml), with 2N KOH (2×500 ml), and with water (1,000 ml). The material was dried over magnesium sulfate, filtered, and the solvent evaporated. The crude product was distilled in vacuo, yielding approximately 155.36 g (1.05 mol). The boiling point is 110° C. at 1.5 mm Hg. The solution was then washed with 2N HCl (4×1,000 ml), with 2N KOH (2×500 ml) The material was dried over magnesium sulfate filtered the solvent evaporated The crude product was distilled in vacuo yielding approximately 155.36 g (1.05 mol)

反应条件: temp:111.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The crude product 2 was placed into a 5-liter 3-necked round-bottomed flask equipped with a mechanical stirrer and a water trap. Toluene (1,900 ml) was added and the solution heated at reflux temperature (111° C.) until all water had been removed. Diazabicyclounde-7-ene (DBU) (65 g) was then added and the mixture was stirred at 111° C., without the water trap, until the starting material was no longer present, i.e., was not detectable by TLC monitoring. Most of the solvent (90%) was then distilled off. The residue was cooled to 25° C., and ethyl acetate (1,000 ml) was added. The mixture was transferred to a separatory funnel and the organic solution washed with 2N HCl (2×1,000 ml), then with water (1,000 ml). Drying was done over magnesium sulfate. The crude product (326.56 g) was a dark oil and was used directly in the next step. A small sample was purified for the purpose of structure elucidation: the crude material (2 g) was dissolved in ethyl ether and washed with 1N KOH. Drying was done over magnesium sulfate, the material was filtered, and the solvent evaporated. The oily residue was crystallized from isopropanol. The melting range is 53.8°-54° C. equipped with a mechanical stirrer and a water trap the solution heated had been removed Diazabicyclounde-7-ene (DBU) (65 g) was then added Most of the solvent (90%) was then distilled off The residue was cooled to 25° C. ethyl acetate (1,000 ml) was added The mixture was transferred to a separatory funnel the organic solution washed with 2N HCl (2×1,000 ml) Drying A small sample was purified for the purpose of structure elucidation the crude material (2 g) was dissolved in ethyl ether washed with 1N KOH Drying the material was filtered the solvent evaporated The oily residue was crystallized from isopropanol

反应条件: temp:111.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The crude product 2 was placed into a 5-liter 3-necked round-bottomed flask equipped with a mechanical stirrer and a water trap. Toluene (1,900 ml) was added and the solution heated at reflux temperature (111° C.) until all water had been removed. Diazabicyclounde-7-ene (DBU) (65 g) was then added and the mixture was stirred at 111° C., without the water trap, until the starting material was no longer present, i.e., was not detectable by TLC monitoring. Most of the solvent (90%) was then distilled off. The residue was cooled to 25° C., and ethyl acetate (1,000 ml) was added. The mixture was transferred to a separatory funnel and the organic solution washed with 2N HCl (2×1,000 ml), then with water (1,000 ml). Drying was done over magnesium sulfate. The crude product (326.56 g) was a dark oil and was used directly in the next step. A small sample was purified for the purpose of structure elucidation: the crude material (2 g) was dissolved in ethyl ether and washed with 1N KOH. Drying was done over magnesium sulfate, the material was filtered, and the solvent evaporated. The oily residue was crystallized from isopropanol. The melting range is 53.8°-54° C. equipped with a mechanical stirrer and a water trap the solution heated had been removed Diazabicyclounde-7-ene (DBU) (65 g) was then added Most of the solvent (90%) was then distilled off The residue was cooled to 25° C. ethyl acetate (1,000 ml) was added The mixture was transferred to a separatory funnel the organic solution washed with 2N HCl (2×1,000 ml) Drying A small sample was purified for the purpose of structure elucidation the crude material (2 g) was dissolved in ethyl ether washed with 1N KOH Drying the material was filtered the solvent evaporated The oily residue was crystallized from isopropanol

反应条件: temp:111.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The crude product 2 was placed into a 5-liter 3-necked round-bottomed flask equipped with a mechanical stirrer and a water trap. Toluene (1,900 ml) was added and the solution heated at reflux temperature (111° C.) until all water had been removed. Diazabicyclounde-7-ene (DBU) (65 g) was then added and the mixture was stirred at 111° C., without the water trap, until the starting material was no longer present, i.e., was not detectable by TLC monitoring. Most of the solvent (90%) was then distilled off. The residue was cooled to 25° C., and ethyl acetate (1,000 ml) was added. The mixture was transferred to a separatory funnel and the organic solution washed with 2N HCl (2×1,000 ml), then with water (1,000 ml). Drying was done over magnesium sulfate. The crude product (326.56 g) was a dark oil and was used directly in the next step. A small sample was purified for the purpose of structure elucidation: the crude material (2 g) was dissolved in ethyl ether and washed with 1N KOH. Drying was done over magnesium sulfate, the material was filtered, and the solvent evaporated. The oily residue was crystallized from isopropanol. The melting range is 53.8°-54° C. equipped with a mechanical stirrer and a water trap the solution heated had been removed Diazabicyclounde-7-ene (DBU) (65 g) was then added Most of the solvent (90%) was then distilled off The residue was cooled to 25° C. ethyl acetate (1,000 ml) was added The mixture was transferred to a separatory funnel the organic solution washed with 2N HCl (2×1,000 ml) Drying A small sample was purified for the purpose of structure elucidation the crude material (2 g) was dissolved in ethyl ether washed with 1N KOH Drying the material was filtered the solvent evaporated The oily residue was crystallized from isopropanol

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of methyl 2-methyl-3-oxononanoate (3.06 g) in THF (5 ml) was added to a suspension of 60% NaH (608 mg) in THF (30 ml) while cooling on ice, and the mixture was stirred at 0° C. for 10 minutes and then at room temperature for 30 minutes. The reaction solution was cooled to −78° C., 1.66 M n-BuLi (9.2 ml) was added, and the mixture was stirred at −78° C. for 30 minutes to prepare a dienolate. A solution of methyl 2-benzofurancarboxylate (1.25 g) in THF (5 ml) was added to the dienolate, and the mixture was stirred at −78° C. for 30 minutes. The reaction solution was brought to 0° C., an NH4Cl aqueous solution was added for quenching, and extraction was performed with AcOEt. The organic layer was rinsed with water and saturated saline in that order, and then dried with Na2SO4, filtered and concentrated. The residue was dissolved in MeOH (50 ml), and after adding 2N-LiOH (30 ml) and stirring at room temperature for 2 hours, 1N-HCl was added at 0° C. to acidity of approximately pH 3, and extraction was performed with AcOEt. The organic layer was rinsed with water and saturated saline in that order, and then dried with Na2SO4, filtered and concentrated. Pyridine (20 ml) and Ac2O (20 ml) were added to the residue, and after stirring the mixture at room temperature for 5 hours it was concentrated under reduced pressure. The residue was dissolved in MeOH (20 ml), imidazole (483 mg) was added at 0° C., and after stirring the mixture at 0° C. for 10 minutes and then at room temperature for 30 minutes, it was concentrated under reduced pressure. AcOEt was added to the residue, and the precipitated crystals were filtered off. The crystals were recrystallized from EtOH to obtain 6-(benzofuran-2-yl)-4-hydroxy-3-methyl-5-n-pentyl-2H-pyran-2-one. while cooling on ice at room temperature for 30 minutes The reaction solution was cooled to −78° C. the mixture was stirred at −78° C. for 30 minutes to prepare a dienolate the mixture was stirred at −78° C. for 30 minutes was brought to 0° C. for quenching extraction The organic layer was rinsed with water and saturated saline in that order dried with Na2SO4 filtered concentrated The residue was dissolved in MeOH (50 ml) after adding 2N-LiOH (30 ml) stirring at room temperature for 2 hours 1N-HCl was added at 0° C. to acidity of approximately pH 3, and extraction The organic layer was rinsed with water and saturated saline in that order dried with Na2SO4 filtered concentrated Pyridine (20 ml) and Ac2O (20 ml) were added to the residue after stirring the mixture at room temperature for 5 hours it was concentrated under reduced pressure The residue was dissolved in MeOH (20 ml) imidazole (483 mg) was added at 0° C. after stirring the mixture at 0° C. for 10 minutes at room temperature for 30 minutes it was concentrated under reduced pressure AcOEt was added to the residue the precipitated crystals were filtered off The crystals were recrystallized from EtOH

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: After adding 60% NaH (220 mg) to a solution of methyl 2-methyl-3-oxopentanoate (750 mg) in THF (5 ml) at 0° C. and stirring at 0° C. for 5 minutes, the mixture was cooled to −78° C. To this reaction solution there was added 1.63 M n-BuLi (3.3 ml), and the mixture was stirred at −78° C. for 30 minutes to prepare a dienolate. A solution of methyl 2-benzofurancarboxylate (300 mg) in THF (10 ml) was added to the dienolate, and the mixture was stirred at −78° C. for 20 minutes. The reaction solution was allowed to return to 0° C., aqueous KHSO4 was added for quenching, and extraction was performed with AcOEt. The organic layer was rinsed with saturated saline and dried with MgSO4, and then filtered and concentrated. The residue was crudely purified by silica gel column chromatography (n-hexane/AcOEt=3/1→2/1) to obtain methyl 5-(benzofuran-2-yl)-2,4-dimethyl-3,5-dioxopentanoate. the mixture was cooled to −78° C the mixture was stirred at −78° C. for 30 minutes to prepare a dienolate the mixture was stirred at −78° C. for 20 minutes to return to 0° C. for quenching extraction The organic layer was rinsed with saturated saline dried with MgSO4 filtered concentrated The residue was crudely purified by silica gel column chromatography (n-hexane/AcOEt=3/1→2/1)

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

实验步骤: After adding thionyl chloride (3.80 ml) to a solution of 2-benzofurancarboxylic acid (2.00 g) in MeOH (60 ml) at −40° C., the mixture was stirred for 19 hours while the temperature gradually increased to room temperature. The reaction solution was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (n-hexane/AcOEt=6/1) to obtain methyl 2-benzofurancarboxylate. The reaction solution was concentrated under reduced pressure the residue was purified by silica gel column chromatography (n-hexane/AcOEt=6/1)

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

实验步骤: To a solution of 2-benzofuranoic acid methyl ester in carbon disulphide (240 ml) cooled to 5° C. was added acetyl chloride (70 ml) followed portionwise over 1 hour by aluminium trichloride (40 g). The mixture was heated under reflux for 42 hours before cooling and decanting the carbon disulphide. The residual complex was destroyed by the addition of iced water (50 ml) and 2N HCl (50 ml). The resulting mixture was extracted with ethyl acetate (3×200 ml). The organic layers were combined, washed with water (100 ml), dried (MgSO4) and concentrated. The residue was purified by flash column chromatography, eluting with ethyl acetate/hexane (10:90 to 40:60, v/v), to give methyl 5-acetylbenzofuran-2-carboxylate as a solid (3.099 g); NMR 2.68 (3H,s), 4.00(3H,s), 7.6-8.35(4H,m). The mixture was heated under reflux for 42 hours before cooling decanting the carbon disulphide The residual complex was destroyed by the addition of iced water (50 ml) and 2N HCl (50 ml) The resulting mixture was extracted with ethyl acetate (3×200 ml) washed with water (100 ml) dried (MgSO4) concentrated The residue was purified by flash column chromatography eluting with ethyl acetate/hexane (10:90 to 40:60

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

实验步骤: To a solution of 2-benzofuranoic acid methyl ester in carbon disulphide (240 ml) cooled to 5° C. was added acetyl chloride (70 ml) followed portionwise over 1 hour by aluminium trichloride (40 g). The mixture was heated under reflux for 42 hours before cooling and decanting the carbon disulphide. The residual complex was destroyed by the addition of iced water (50 ml) and 2N HCl (50 ml). The resulting mixture was extracted with ethyl acetate (3×200 ml). The organic layers were combined, washed with water (100 ml), dried (MgSO4) and concentrated. The residue was purified by flash column chromatography, eluting with ethyl acetate/hexane (10:90 to 40:60, v/v), to give methyl 5-acetylbenzofuran-2-carboxylate as a solid (3.099 g); NMR 2.68(3H,s), 4.00(3H,s), 7.6-8.35(4H,m). The mixture was heated under reflux for 42 hours before cooling decanting the carbon disulphide The residual complex was destroyed by the addition of iced water (50 ml) and 2N HCl (50 ml) The resulting mixture was extracted with ethyl acetate (3×200 ml) washed with water (100 ml) dried (MgSO4) concentrated The residue was purified by flash column chromatography eluting with ethyl acetate/hexane (10:90 to 40:60

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

实验步骤: To a solution of 2-benzofuranoic acid methyl ester in carbon disulphide (240 ml) cooled to 5° C. was added acetyl chloride (70 ml) followed portionwise over 1 hour by aluminium trichloride (40 g). The mixture was heated under reflux for 42 hours before cooling and decanting the carbon disulphide. The residual complex was destroyed by the addition of iced water (50 ml) and 2N HCl (50 ml). The resulting mixture was extracted with ethyl acetate (3×200 ml). The organic layers were combined, washed with water (100 ml), dried (MgSO4) and concentrated. The residue was purified by flash column chromatography, eluting with ethyl acetate / hexane (10:90 to 40:60, v/v), to give methyl 5-acetylbenzofuran-2-carboxylate as a solid (3.099 g); NMR 2.68 (3H,s), 4.00(3H,s), 7.6-8.35(4H,m). The mixture was heated under reflux for 42 hours before cooling decanting the carbon disulphide The residual complex was destroyed by the addition of iced water (50 ml) and 2N HCl (50 ml) The resulting mixture was extracted with ethyl acetate (3×200 ml) washed with water (100 ml) dried (MgSO4) concentrated The residue was purified by flash column chromatography eluting with ethyl acetate / hexane (10:90 to 40:60