苯并呋喃-3-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 stirring solution of 650 mg (3.69 mmol) of Benzofuran-3-carboxylic acid methyl ester, prepared as in Intermediate 18, in 25 mL dichloromethane at -78° C. is added dropwise over 5 min a solution of 9.22 mL (9.22 mmol, 2.5 equiv) of a 1.0M solution of DIBAL-H in hexane. The resulting solution is allowed to slowly warm to RT over a 4 h period then quenched by careful addition of 5 mL of H2O. The reaction mixture is poured into 100 mL of EtOAc and extracted with 1N HCl (1×100 mL), dried (MgSO4), and the solvent removed in vacuo. Purification of the crude material by silica gel flash column chromatography using hexane/EtOAc 4/1 as eluent afforded 444 mg of the title compound as a pale yellow oil: 1H NMR (CDCl3, 300 MHz) δ7.66 (d, 1H), 7.60 (s, 1H), 7.49 (d, 1H), 7.29 (m, 2H), 4.82 (d, 2H), 1.70 (m, 1H); Rf =0.17 in hexane/EtOAc 5/1. then quenched by careful addition of 5 mL of H2O The reaction mixture is poured into 100 mL of EtOAc extracted with 1N HCl (1×100 mL) dried (MgSO4) the solvent removed in vacuo Purification of the crude material by silica gel flash column chromatography

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A stirring solution of 2.43 g (9.45 mmol) of 3-(2-Bromo-phenoxy) acrylic acid methyl ester, prepared as in Intermediate 17, 1.98 g (7.56 mmol, 0.8 equiv) of triphenylphosphine, 794 mg (9.45 mmol, 1.0 equiv) of NaHCO3, and 848 mg (3.78 mmol, 0.4 equiv) of palladium (II) acetate in 25 mL of DMF is heated to 110° C. for 16 h. After cooling to RT, the reaction mixture is diluted with 100 mL of Et2O and extracted with H2O (1×100 mL), dried (MgSO4), and the solvents removed in vacuo. Purification of the crude material by silica gel flash column chromatography afforded 650 mg of the title compound as a yellow oil: 1H NMR (CDCl3, 300 MHz) δ8.22 (s, 1H), 8.06 (m, 1H), 7.55 (m, 1H), 7.37 (m, 2H), 3.95 (s, 3H); Rf =0.50 in hexane/EtOAc 5/1. After cooling to RT extracted with H2O (1×100 mL) dried (MgSO4) the solvents removed in vacuo Purification of the crude material by silica gel flash column chromatography

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

实验步骤: To a methanol (30 mL) solution of 1-benzofuran-3-carboxylic acid methyl ester (5.25 g, 29.8 mmol) tetrahydrofuran (60 mL), water (30 mL) and lithium hydroxide (2.50 g, 59.9 mmol) were added at room temperature. The mixture was stirred for 15 hours at room temperature. 1N-hydrochloric acid (60 mL, 60 mmol) was added to the reaction liquor, and then methanol was distilled off under reduced pressure. 1N-hydrochloric acid (15 mL, 15 mmol) was added to the obtained aqueous layer, and solids generated therefrom were collected by filtration. The solids were washed with water, and then dried for two days at 50° C. with a vacuum pump, to obtain the title compound (4.41 g, 27.2 mmol, 91%) as a solid. methanol was distilled off under reduced pressure generated therefrom were collected by filtration The solids were washed with water dried for two days at 50° C. with a vacuum pump

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

实验步骤: To a methanol (30 mL) solution of 1-benzofuran-3-carboxylic acid methyl ester (5.25 g, 29.8 mmol) tetrahydrofuran (60 mL), water (30 mL) and lithium hydroxide (2.50 g, 59.9 mmol) were added at room temperature. The mixture was stirred for 15 hours at room temperature. 1N-hydrochloric acid (60 mL, 60 mmol) was added to the reaction liquor, and then methanol was distilled off under reduced pressure. 1N-hydrochloric acid (15 mL, 15 mmol) was added to the obtained aqueous layer, and solids generated therefrom were collected by filtration. The solids were washed with water, and then dried for two days at 50° C. with a vacuum pump, to obtain the title compound (4.41 g, 27.2 mmol, 91%) as a solid. methanol was distilled off under reduced pressure generated therefrom were collected by filtration The solids were washed with water dried for two days at 50° C. with a vacuum pump

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a DMF (8.0 mL) solution of 1-benzofuran-3-yl trifluoromethanesulfonic acid (1.00 g, 3.76 mmol), 1,1′-diphenylphosphinoferrocene (128 mg, 231 μmol) and palladium acetate (26.0 mg, 116 μmol), methanol (3.5 mL) and triethylamine (1.05 mL, 7.53 mmol) were added thereto at room temperature. Carbon monoxide gas was bubbled for 20 minutes, and then under a carbon monoxide atmosphere, the mixture was heated and stirred at 60° C. for 3 hours. Water (50 mL) was added, and then the mixture was extracted with ethyl acetate (2×30 mL). The organic layer was combined, washed with 1N-hydrochloric acid (30 mL), and then dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure. The obtained residue was purified using silica gel flash column chromatography (Biotage AB: column No. 40M, hexane:diethyl ether=95:5), to obtain the title compound (570 mg, 3.24 mmol, 86%) as a transparent oily matter. at room temperature Carbon monoxide gas was bubbled for 20 minutes under a carbon monoxide atmosphere, the mixture was heated Water (50 mL) was added the mixture was extracted with ethyl acetate (2×30 mL) washed with 1N-hydrochloric acid (30 mL) dried over anhydrous magnesium sulfate The solvent was concentrated under reduced pressure The obtained residue was purified

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

实验步骤: To a stirring solution of 650 mg (3.69 mmol) of Benzofuran-3-carboxylic acid methyl ester, prepared as in Intermediate 18, in 25 mL dichloromethane at -78° C. is added dropwise over 5 min a solution of 9.22 mL (9.22 mmol, 2.5 equiv) of a 1.0M solution of DIBAL-H in hexane. The resulting solution is allowed to slowly warm to RT over a 4 h period then quenched by careful addition of 5 mL of H2O. The reaction mixture is poured into 100 mL of EtOAc and extracted with 1N HCl (1×100 mL), dried (MgSO4), and the solvent removed in vacuo. Purification of the crude material by silica gel flash column chromatography using hexane/EtOAc 4/1 as eluent afforded 444 mg of the title compound as a pale yellow oil: 1H NMR (CDCl3, 300 MHz) δ7.66 (d, 1H), 7.60 (s, 1H), 7.49 (d, 1H), 7.29 (m, 2H), 4.82 (d, 2H), 1.70 (m, 1H); Rf =0.17 in hexane/EtOAc 5/1. then quenched by careful addition of 5 mL of H2O The reaction mixture is poured into 100 mL of EtOAc extracted with 1N HCl (1×100 mL) dried (MgSO4) the solvent removed in vacuo Purification of the crude material by silica gel flash column chromatography

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

实验步骤: To a stirring solution of 650 mg (3.69 mmol) of Benzofuran-3-carboxylic acid methyl ester, prepared as in Intermediate 18, in 25 mL dichloromethane at -78° C. is added dropwise over 5 min a solution of 9.22 mL (9.22 mmol, 2.5 equiv) of a 1.0M solution of DIBAL-H in hexane. The resulting solution is allowed to slowly warm to RT over a 4 h period then quenched by careful addition of 5 mL of H2O. The reaction mixture is poured into 100 mL of EtOAc and extracted with 1N HCl (1×100 mL), dried (MgSO4), and the solvent removed in vacuo. Purification of the crude material by silica gel flash column chromatography using hexane/EtOAc 4/1 as eluent afforded 444 mg of the title compound as a pale yellow oil: 1H NMR (CDCl3, 300 MHz) δ7.66 (d, 1H), 7.60 (s, 1H), 7.49 (d, 1H), 7.29 (m, 2H), 4.82 (d, 2H), 1.70 (m, 1H); Rf =0.17 in hexane/EtOAc 5/1. then quenched by careful addition of 5 mL of H2O The reaction mixture is poured into 100 mL of EtOAc extracted with 1N HCl (1×100 mL) dried (MgSO4) the solvent removed in vacuo Purification of the crude material by silica gel flash column chromatography

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A stirring solution of 2.43 g (9.45 mmol) of 3-(2-Bromo-phenoxy) acrylic acid methyl ester, prepared as in Intermediate 17, 1.98 g (7.56 mmol, 0.8 equiv) of triphenylphosphine, 794 mg (9.45 mmol, 1.0 equiv) of NaHCO3, and 848 mg (3.78 mmol, 0.4 equiv) of palladium (II) acetate in 25 mL of DMF is heated to 110° C. for 16 h. After cooling to RT, the reaction mixture is diluted with 100 mL of Et2O and extracted with H2O (1×100 mL), dried (MgSO4), and the solvents removed in vacuo. Purification of the crude material by silica gel flash column chromatography afforded 650 mg of the title compound as a yellow oil: 1H NMR (CDCl3, 300 MHz) δ8.22 (s, 1H), 8.06 (m, 1H), 7.55 (m, 1H), 7.37 (m, 2H), 3.95 (s, 3H); Rf =0.50 in hexane/EtOAc 5/1. After cooling to RT extracted with H2O (1×100 mL) dried (MgSO4) the solvents removed in vacuo Purification of the crude material by silica gel flash column chromatography

反应条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diisobutylaluminium hydride in toluene (1.5M, 16.8 ml, 25.2 mmol) was added dropwise to a solution of methyl benzo[b]furan-3-carboxylate (2.02 g, 11.5 mmol) in tetrahydrofuran (50 ml) at -75° C. The resulting solution was stirred at -75° C. for 30 minutes, the cooling bath removed and the mixture allowed to warm to room temperature. The reaction mixture was recooled to -40° C. and quenched by sequential addition of methanol (3 ml), water (1.5 ml) and 2M sodium hydroxide (1.5 ml). The mixture was allowed to warm up to produce a gel, which was filtered off and washed with dichloromethane (6×50 ml). The filtrate was evaporated to dryness, the residue redissolved in ether and the solution dried over magnesium sulfate. The solution was evaporated to afford the title compound (1.66 g, 98%) as an oil which crystallised on standing; δH (CDCl3) 1.61 (1H, br s, OH), 4.85 (2H, s, CH2OH), 7.25-7.35 (2H, m, ArH), 7.49 (1H, dd, J 7.8, 1.0Hz, ArH), 7.61 (1H, s, 2-H), 7.67 (1H, m, ArH). the cooling bath removed to warm to room temperature was recooled to -40° C. quenched by sequential addition of methanol (3 ml), water (1.5 ml) and 2M sodium hydroxide (1.5 ml) to warm up to produce a gel, which was filtered off washed with dichloromethane (6×50 ml) The filtrate was evaporated to dryness the residue redissolved in ether the solution dried over magnesium sulfate The solution was evaporated

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of benzo[b]furan-3-yl trifluoromethanesulfonate (5.00 g, 18.8 mmol), triethylamine (5.2 ml, 37.3 mmol), palladium (II) acetate (0.130 g, 0.579 mmol), 1,1'-bis(diphenylphosphino)ferrocene (0.628 g, 1.13 mmol), and methanol (17 ml) in dimethylformamide (40 ml) was purged with carbon monoxide for 20 minutes and stirred under a carbon monoxide balloon at 60° C. for 2.5 hours. The reaction mixture was allowed to cool, diluted with water (250 ml) and extracted with ethyl acetate (2×100 ml). The extracts were washed with 1M hydrochloric acid (100 ml) then saturated brine (100 ml), combined and dried (magnesium sulfate). The solvent was evaporated and the residue purified by flash chromatography, eluting with 5% ethyl acetate in petrol (60°-80° ) then 10% ethyl acetate in petrol (60°-80° ), to afford the title compound (2.65 g, 80%) as a pale yellow oil; δH (CDCl3) 3.94 (3H, s, CO2CH3), 7.34-7.39 (2H, m, ArH), 7.53 (1H, m, ArH), 8.07 (1H, m, ArH), 8.26 (1H, s, 2-H). was purged with carbon monoxide for 20 minutes to cool diluted with water (250 ml) extracted with ethyl acetate (2×100 ml) The extracts were washed with 1M hydrochloric acid (100 ml) dried (magnesium sulfate) The solvent was evaporated the residue purified by flash chromatography eluting with 5% ethyl acetate in petrol (60°-80° )

反应条件: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diisobutylaluminium hydride in toluene (1.5M, 16.8 ml, 25.2 mmol) was added dropwise to a solution of methyl benzo[b]furan-3-carboxylate (2.02 g, 11.5 mmol) in tetrahydrofuran (50 ml) at -75° C. The resulting solution was stirred at -75° C. for 30 minutes, the cooling bath removed and the mixture allowed to warm to room temperature. The reaction mixture was recooled to -40° C. and quenched by sequential addition of methanol (3 ml), water (1.5 ml) and 2M sodium hydroxide (1.5 ml). The mixture was allowed to warm up to produce a gel, which was filtered off and washed with dichloromethane (6×50 ml). The filtrate was evaporated to dryness, the residue redissolved in ether and the solution dried over magnesium sulphate. The solution was evaporated to afford the title compound (1.66 g, 98%) as an oil which crystallised on standing; δH (CDCl3) 1.61 (1H, br s, OH), 4.85 (2H, s, C H2OH), 7.25-7.35 (2H, m, ArH), 7.49 (1H, dd, J 7.8, 1.0 Hz, ArH), 7.61 (1H, s, 2-H), 7.67 (1H, m, ArH). the cooling bath removed to warm to room temperature was recooled to -40° C. quenched by sequential addition of methanol (3 ml), water (1.5 ml) and 2M sodium hydroxide (1.5 ml) to warm up to produce a gel, which was filtered off washed with dichloromethane (6×50 ml) The filtrate was evaporated to dryness the residue redissolved in ether the solution dried over magnesium sulphate The solution was evaporated

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of benzo[b]furan-3-yl trifluoromethanesulfonate (5.00 g, 18.8 mmol), triethylamine (5.2 ml, 37.3 mmol), palladium (II) acetate (0.130 g, 0.579 mmol), 1, 1'-bis(diphenylphosphino)ferrocene (0.628 g, 1.13 mmol), and methanol (17 ml) in dimethylformamide (40 ml) was purged with carbon monoxide for 20 minutes and stirred under a carbon monoxide balloon at 60° C. for 2.5 hours. The reaction mixture was allowed to cool, diluted with water (250 ml) and extracted with ethyl acetate (2×100 ml). The extracts were washed with 1M hydrochloric acid (100 ml) then saturated brine (100 ml), combined and dried (magnesium sulfate). The solvent was evaporated and the residue purified by flash chromatography, eluting with 5% ethyl acetate in petrol (60°-80°) then 10% ethyl acetate in petrol (60°-80°), to afford the title compound (2.65 g, 80%) as a pale yellow oil; δH (CDCl3) 3.94 (3H, s, CO2CH3), 7.34-7.39 (2H, m, ArH), 7.53 (1H, m, ArH), 8.07 (1H, m, ArH), 8.26 (1H, s, 2-H). was purged with carbon monoxide for 20 minutes to cool diluted with water (250 ml) extracted with ethyl acetate (2×100 ml) The extracts were washed with 1M hydrochloric acid (100 ml) dried (magnesium sulfate) The solvent was evaporated the residue purified by flash chromatography eluting with 5% ethyl acetate in petrol (60°-80°)