3-(吲哚-3-基)丙酸甲酯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

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 3-(1H-indol-3-yl)propanoic acid (0.3 g) in MeCN (9 mL) was added K2CO3 (0.33 g) at ambient temperature followed by addition of iodomethane (0.15 mL). After 3 hours, water was added and the mixture was extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The residue was purified by column chromatography (n-hexane:EtOAc=3:1) to give methyl 3-(1H-indol-3-yl)propanoate (0.32 g). the mixture was extracted with EtOAc The organic layer was washed with brine dried over anhydrous sodium sulfate filtered evaporated in vacuo The residue was purified by column chromatography (n-hexane:EtOAc=3:1)

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

实验步骤: A mixture of methyl 3-indolepropionate (5.00 g, 0.0246 mol), acetic acid (10 mL), dimethylsulfoxide (26 mL, 0.369 mol, 15 eq.) and concentrated hydrogen chloride (37%) (22 mL, 0.738 mol, 30 eq.) was stirred at ambient temperature for 2.5 h. Water was added to the mixture and the mixture was extracted with ethyl acetate. The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified using the Biotage flash chromatography system (30% ethyl acetate in hexanes) to afford the title compound as an oil (5.28 g, 98%); 1H NMR (DMSO-d6); δ2.03-2.10 (m, 2H); 2.32-2.39 (m, 2H); 3.46 (t, J=6.4 Hz, 1H); 3.54 (s, 3H); 6.81 (d, J=7.6 Hz, 1H); 6.93-6.97 (m, 1H); 7.15-7.17 (m, 1H); 7.24 (d, J=7.6 Hz, 1H); the mixture was extracted with ethyl acetate The organic layer was dried over MgSO4 filtered concentrated in vacuo The crude residue was purified

反应条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Sodium hydride (60% dispersion) (236 mg, 5.91 mmol, 1.2 equiv) was slowly added to a cold mixture of methyl 3-(1H-indol-3-yl)propanoate (2 g, 4.92 mmol, 1 equiv) in N,N-dimethylformamide. After all the sodium hydride has reacted, 1-bromo-3-chloropropane (1.94 ml, 19.68 mmol, 4 equiv) was added and the reaction stirred at 55° C. for 16 h. Upon cooling the reaction was partitioned between water and ethyl acetate. The organic layer was further washed with 1N hydrogen chloride, brine, dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified using the Biotage flash chromatography system (SNAP 50 g cartridge, Rf=0.5, gradient—1%-10% ethyl acetate in hexanes) to afford the title compound as a yellow oil (1.154 g, 83%); 1H NMR (400 MHz, DMSO-d6): δ 2.12-2.27 (m, 2H); 2.65-2.70 (m, 2H); 2.93-2.98 (m, 2H); 3.38-3.54 (m, 2H); 3.58 (s, 3H); 4.08-4.12 (m, 2H); 4.21-4.25 (m, 2H); 7.02 (t, 1H, J=7.6 Hz); 7.12-7.15 (m, 2H); 7.43 (dd, 1H, J=3.2 and 2.8 Hz); 7.52-7.55 (m, 1H); MS for C15H18ClNO2 m/z 280 (M+H)+. Upon cooling the reaction was partitioned between water and ethyl acetate The organic layer was further washed with 1N hydrogen chloride, brine dried over MgSO4 filtered concentrated in vacuo The crude residue was purified

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

实验步骤: 2 g (10.57 mmol) of 3-indolepropionic acid were dissolved in 50 ml of methanol. The solution was cooled to 0° C. and 5 ml of sulfuric acid 96% were dropped under stirring. The solution was maintained at room temperature overnight and then poured onto ice-water, basified with 30% ammonium hydrate and finally extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate and evaporated to dryness to give 2.3 g of an oily product (93% yield). The solution was maintained at room temperature overnight poured onto ice-water finally extracted with methylene chloride The organic layer was dried over anhydrous sodium sulfate evaporated to dryness

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

实验步骤: A mixture of methyl 3-indolepropionate (5.00 g, 0.0246 mol), acetic acid (10 mL), dimethylsulfoxide (26 mL, 0.369 mol, 15 eq.) and concentrated hydrogen chloride (37%) (22 mL, 0.738 mol, 30 eq.) was stirred at ambient temperature for 2.5 h. Water was added to the mixture and the mixture was extracted with ethyl acetate. The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified using the Biotage flash chromatography system (30% ethyl acetate in hexanes) to afford the title compound as an oil (5.28 g, 98%); 1H NMR (DMSO-d6); 62.03-2.10 (m, 2H); 2.32-2.39 (m, 2H); 3.46 (t, J=6.4 Hz, 1H); 3.54 (s, 3H); 6.81 (d, J=7.6 Hz, 1H); 6.93-6.97 (m, 1H); 7.15-7.17 (m, 1H); 7.24 (d, J=7.6 Hz, 1H); the mixture was extracted with ethyl acetate The organic layer was dried over MgSO4 filtered concentrated in vacuo The crude residue was purified

反应条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Sodium hydride (60% dispersion) (236 mg, 5.91 mmol, 1.2 equiv) was slowly added to a cold mixture of methyl 3-(1H-indol-3-yl)propanoate (2 g, 4.92 mmol, 1 equiv) in N,N-dimethylformamide. After all the sodium hydride has reacted, 1-bromo-3-chloropropane (1.94 ml, 19.68 mmol, 4 equiv) was added and the reaction stirred at 55° C. for 16 h. Upon cooling the reaction was partitioned between water and ethyl acetate. The organic layer was further washed with 1N hydrogen chloride, brine, dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified using the Biotage flash chromatography system (SNAP 50 g cartridge, Rf=0.5, gradient—1%-10% ethyl acetate in hexanes) to afford the title compound as a yellow oil (1.154 g, 83%); 1H NMR (400 MHz, DMSO-d6): δ 2.12-2.27 (m, 2H); 2.65-2.70 (m, 2H); 2.93-2.98 (m, 2H); 3.38-3.54 (m, 2H); 3.58 (s, 3H); 4.08-4.12 (m, 2H); 4.21-4.25 (m, 2H); 7.02 (t, 1H, J=7.6 Hz); 7.12-7.15 (m, 2H); 7.43 (dd, 1H, J=3.2 and 2.8 Hz); 7.52-7.55 (m, 1H); MS for C15H18ClNO2 m/z 280 (M+H)+. Upon cooling the reaction was partitioned between water and ethyl acetate The organic layer was further washed with 1N hydrogen chloride, brine dried over MgSO4 filtered concentrated in vacuo The crude residue was purified

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

实验步骤: 36.2 g of powdered potassium carbonate was added, with ice-cooling, to a solution of 24.8 g of 3-(indol-3-yl)propionic acid in 500 ml of N,N-dimethylformamide, followed by the addition of a solution of 10.2 ml methyl iodide in 50 ml of N,N-dimethylformamide. The reaction mixture was then warmed to room temperature and stirred for 3 hours. After this time, ice water was added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate. The organic extract was then washed with water, dried over anhydrous magnesium sulfate and concentrated by evaporation under reduced pressure. The resulting residue was subjected to column chromatography using 500 g of silica gel with a 4:1 v/v mixture of hexane and ethyl acetate as the eluent, to yield 25.8 g of the title compound as an amorphous solid. the aqueous layer was extracted with ethyl acetate The organic extract was then washed with water dried over anhydrous magnesium sulfate concentrated by evaporation under reduced pressure with a 4:1 v/v mixture of hexane and ethyl acetate as the eluent

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

实验步骤: 3-Indolepropionic acid (5 g) was dissolved in MeOH (50 mL) and treated with conc. HCl (5 mL). The solution was stirred overnight before the solvent was removed under reduced pressure to provide methyl 3-indolepropionate in quantitative yield. Crude methyl 3-indolepropionate (4.70 g, 23.2 mmol) was dissolved in THF (50 mL), cooled to 0° C., and treated with DIBAL-H (69.5 mL, 69.5 mmol). The reaction mixture was stirred for 2 h at 0° C. and then quenched by the slow addition of a saturated aqueous solution of ammonium chloride and extracted with ethyl acetate, the combined organic extracts were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with 1:1 ethyl acetate/hexane, afforded the 3-(3-hydroxypropyl)indole as a yellow solid. 1H NMR (200 MHz, DMSO-d6) δ 7.48 (d, J=8.0 Hz, 1H), 7.23 (d, J=8.0 Hz, 1H), 7.15–6.92 (m, 4H), 4.40 (t, J=6.0 Hz, 1H), 3.55 (t, J=6.0 Hz, 2H), 2.80 (t, J=8.0 Hz, 2H), 1.92–1.76 (m, 2H). quenched by the slow addition of a saturated aqueous solution of ammonium chloride extracted with ethyl acetate the combined organic extracts were washed with brine dried over MgSO4 filtered concentrated under reduced pressure Purification by silica gel chromatography eluting with 1:1 ethyl acetate/hexane

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

实验步骤: 3-Indolepropionic acid (5 g) was dissolved in MeOH (50 mL) and treated with conc. HCl (5 mL). The solution was stirred overnight before the solvent was removed under reduced pressure to provide methyl 3-indolepropionate in quantitative yield. Crude methyl 3-indolepropionate (4.70 g, 23.2 mmol) was dissolved in THF (50 mL), cooled to 0° C., and treated with DIBAL-H (69.5 mL, 69.5 mmol). The reaction mixture was stirred for 2 h at 0° C. and then quenched by the slow addition of a saturated aqueous solution of ammonium chloride and extracted with ethyl acetate, the combined organic extracts were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with 1:1 ethyl acetate/hexane, afforded the 3-(3-hydroxypropyl)indole as a yellow solid. 1H NMR (200 MHz, DMSO-d6) δ 7.48 (d, J=8.0 Hz, 1H), 7.23 (d, J=8.0 Hz, 1H), 7.15–6.92 (m, 4H), 4.40 (t, J=6.0 Hz, 1H), 3.55 (t, J=6.0 Hz, 2H), 2.80 (t, J=8.0 Hz, 2H), 1.92–1.76 (m, 2H). was removed under reduced pressure