ethyl 3-(1H-indol-3-yl)propanoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(1H-Indol-3-yl)-propionic acid ethyl ester (4.30 g, 1 eq) and hydrazine hydrate (˜9.6 ml, 10 eq) in ethanol (70 ml) is heated at 60° C. overnight. The reaction mixture is concentrated under reduced pressure and diluted with methylene chloride. The new organic solution is washed with water, dried over MgSO4, filtered and evaporated to dryness, to afford the title compound as white solid (3.9 g, 98% yield), which is used as such for the next step. The reaction mixture is concentrated under reduced pressure diluted with methylene chloride The new organic solution is washed with water dried over MgSO4 filtered evaporated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 3-indolepropionic acid (4.00 g, 1 eq) in ethanol (70 ml), 1 ml of sulphuric acid is added dropwise and the mixture is first refluxed overnight and then evaporated to dryness. The resulting crude residue is dissolved in ethyl acetate and the organic solution is washed with 5% aqueous sodium bicarbonate, water, dried over MgSO4, filtered and finally evaporated to dryness, to afford the title compound as a yellow solid (4.30 g, 95% yield), which is used as such for the next step. is added dropwise the mixture is first refluxed overnight evaporated to dryness The resulting crude residue is dissolved in ethyl acetate the organic solution is washed with 5% aqueous sodium bicarbonate, water dried over MgSO4 filtered finally evaporated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 7.38 g of 3-indolepropionic acid and 5.9 g of thionyl chloride in 50 ml of ethanol is refluxed for 2 hours, cooled and evaporated. The residue is partitioned between ether and cold sodium bicarbonate solution. The organic phase is separated, dried over sodium sulfate and evaporated to yield ethyl 3-(3-indolyl)propionate; Rf (ether/SiO2)=0.51; IR (CH2Cl2) 1725 cm-1. cooled evaporated The residue is partitioned between ether and cold sodium bicarbonate solution The organic phase is separated dried over sodium sulfate evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 7.38 g of 3-indolepropionic acid and 5.9 g of thionyl chloride in 50 ml of ethanol is refluxed for 2 hours, cooled and evaporated. The residue is partitioned between ether and cold sodium bicarbonate solution. The organic phase is separated, dried over sodium sulfate and evaporated to yield ethyl 3-(3-indolyl)propionate; Rf (ether/SiO2)=0.51; IR (CH2Cl2) 1725 cm-1. cooled evaporated The residue is partitioned between ether and cold sodium bicarbonate solution The organic phase is separated dried over sodium sulfate evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 8.0 g of ethyl 3-(3-indolyl)propionate and 6.3 g of 3-bromopyridine in 100 ml of pyridine is refluxed with 5.0 g of copper oxide and 10 g of anhydrous potassium carbonate for 48 hours. Evaporation and chromatography on 300 g of silica with 1:1 ethyl ether:hexane as eluant yields 3-[2-(ethoxycarbonyl)ethyl]-N-(3-pyridyl)indole as an oil; Rf =0.2, IR (CH2Cl2) 1725 cm-1. Evaporation and chromatography on 300 g of silica with 1:1 ethyl ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-(1H-Indol-3-yl)-propionic acid ethyl ester (4.30 g, 1 eq) and hydrazine hydrate (˜9.6 ml, 10 eq) in ethanol (70 ml) is heated at 60° C. overnight. The reaction mixture is concentrated under reduced pressure and diluted with methylene chloride. The new organic solution is washed with water, dried over MgSO4, filtered and evaporated to dryness, to afford the title compound as white solid (3.9 g, 98% yield), which is used as such for the next step. The reaction mixture is concentrated under reduced pressure diluted with methylene chloride The new organic solution is washed with water dried over MgSO4 filtered evaporated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 3-indolepropionic acid (4.00 g, 1 eq) in ethanol (70 ml), 1 ml of sulphuric acid is added dropwise and the mixture is first refluxed overnight and then evaporated to dryness. The resulting crude residue is dissolved in ethyl acetate and the organic solution is washed with 5% aqueous sodium bicarbonate, water, dried over MgSO4, filtered and finally evaporated to dryness, to afford the title compound as a yellow solid (4.30 g, 95% yield), which is used as such for the next step. is added dropwise the mixture is first refluxed overnight evaporated to dryness The resulting crude residue is dissolved in ethyl acetate the organic solution is washed with 5% aqueous sodium bicarbonate, water dried over MgSO4 filtered finally evaporated to dryness

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (60% oil 19.03 g 0.476 mol) was washed with n-hexane, and was suspended in DMF (500 ml). To the suspension was gradually added a solution of ethyl indole-3-propionate acid (64.79 g 0.317 mol) in DMF(100 ml). The mixture was stirred for one hour at 40°-50° C., and to the mixture was gradually added, under ice-cooling, 2,4,6-triisopropylphenylsulfonyl chloride (115.25 g, 0.38 mol), followed by stirring for one hour at room temperature. To the reaction mixture was added water (150 ml), and the mixture was subjected to extraction with n-hexane (500 ml). The extract solution was washed with water (100 ml) and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to to leave the title compound (152 g). to the mixture was gradually added, under ice- cooling by stirring for one hour at room temperature the mixture was subjected to extraction with n-hexane (500 ml) The extract solution was washed with water (100 ml) dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (60% oil 19.03 g 0.476 mol) was washed with n-hexane, and was suspended in DMF (500 ml). To the suspension was gradually added a solution of ethyl indole-3-propionate acid (64.79 g 0.317 mol) in DMF(100 ml). The mixture was stirred for one hour at 40°-50° C., and to the mixture was gradually added, under ice-cooling, 2,4,6-triisopropylphenylsulfonyl chloride (115.25 g, 0.38 mol), followed by stirring for one hour at room temperature. To the reaction mixture was added water (150 ml), and the mixture was subjected to extraction with n-hexane (500 ml). The extract solution was washed with water (100 ml) and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to to leave the title compound (152 g). to the mixture was gradually added, under ice- cooling by stirring for one hour at room temperature the mixture was subjected to extraction with n-hexane (500 ml) The extract solution was washed with water (100 ml) dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (60% dispersion in oil, 0.38 g) was added to the mixed solution of ethyl 3-(indol-3-yl)propionate (1.8 g) in DMF (20 ml) and THF (20 ml) under ice-cooling. The reaction mixture was stirred at room temperature for 10 minutes, to which were added 2,4-dichlorobenzyl bromide (1.8 g) and sodium iodide (0.3 g). The reaction mixture was stirred at room temperature for 3 hours and then poured into water, and the mixture was extracted with IPE. The organic layer was washed with water, then dried and concentrated. The residue was dissolved in ethanol (30 ml), which was stirred at 50° C. for 2 hours in the presence of water (10 ml) and sodium hydroxide (1 g). The reaction mixture was concentrated, made acidic, and then extracted with ethyl acetate. The organic layer was washed with water, then dried and concentrated. The residue was recrystallized from ethyl acetate-IPE to obtain the entitled compound (2.4 g). cooling The reaction mixture was stirred at room temperature for 3 hours the mixture was extracted with IPE The organic layer was washed with water dried concentrated The residue was dissolved in ethanol (30 ml) which was stirred at 50° C. for 2 hours in the presence of water (10 ml) and sodium hydroxide (1 g) The reaction mixture was concentrated extracted with ethyl acetate The organic layer was washed with water dried concentrated The residue was recrystallized from ethyl acetate-IPE

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (60% dispersion in oil, 0.38 g) was added to the mixed solution of ethyl 3-(indol-3-yl)propionate (1.8 g) in DMF (20 ml) and THF (20 ml) under ice-cooling. The reaction mixture was stirred at room temperature for 10 minutes, to which were added 2,4-dichlorobenzyl bromide (1.8 g) and sodium iodide (0.3 g). The reaction mixture was stirred at room temperature for 3 hours and then poured into water, and the mixture was extracted with IPE. The organic layer was washed with water, then dried and concentrated. The residue was dissolved in ethanol (30 ml), which was stirred at 50° C. for 2 hours in the presence of water (10 ml) and sodium hydroxide (1 g). The reaction mixture was concentrated, made acidic, and then extracted with ethyl acetate. The organic layer was washed with water, then dried and concentrated. The residue was recrystallized from ethyl acetate-IPE to obtain the entitled compound (2.4 g). cooling The reaction mixture was stirred at room temperature for 3 hours the mixture was extracted with IPE The organic layer was washed with water dried concentrated The residue was dissolved in ethanol (30 ml) which was stirred at 50° C. for 2 hours in the presence of water (10 ml) and sodium hydroxide (1 g) The reaction mixture was concentrated extracted with ethyl acetate The organic layer was washed with water dried concentrated The residue was recrystallized from ethyl acetate-IPE