ethyl 2-(1H-indol-2-yl)acetate

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

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

Procedure: A mixture of ethyl 4-(2-nitrophenyl)-3-oxobutanoate (17.04 g, 67.8 mmol), 10% palladium on carbon (3.6 g), and ethanol (280 mL) was placed under hydrogen pressure (50 psi, 3.4×105 Pa) on a Parr apparatus for 96 hours. The reaction mixture was filtered through a layer of CELITE filter aid. The filtrate was concentrated under reduced pressure to provide crude ethyl 1H-indol-2-ylacetate. for 96 hours The reaction mixture was filtered through a layer of CELITE filter aid The filtrate was concentrated under reduced pressure

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

Procedure: In step (1) of Reaction Scheme VII, ethyl 1H-indol-2-ylacetate is reacted with ethyl chlorooxoacetate to provide ethyl (2-ethoxycarbonylmethyl-1H-indol-3-yl)oxoacetate. The reaction can be carried out using the general method described in step (1) of Reaction Scheme I. Ethyl 1H-indol-2-ylacetate is known.

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

Procedure: Ester 4-1 (0.54 g, 2.6 mmol) was dissolved in 13 mL CH2Cl2 at -78°, and DIBAL (1M in CH2Cl2, 5.8 ml, 5.8 mmol) was added dropwise. The mixture was stirred at -78° for 15 min then warmed to RT for 30 min and quenched in sat. aqueous Na/K tartrate. This solution was extracted with EtOAc. The organic layer was washed with brine, dried (Na2SO4), and concentrated. Flash chromatography (silica 50% EtOAc/hexane) provided 4-2 as a brown oil. Rf 0.38 (silica, 50% EtOAc/hexane). quenched in sat. aqueous Na/K tartrate This solution was extracted with EtOAc The organic layer was washed with brine dried (Na2SO4) concentrated

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

Procedure: Ester 4-1 (0.54 g, 2.6 mmol) was dissolved in 13 mL CH2Cl2 at -78°, and DIBAL (1M in CH2Cl2, 5.8 ml, 5.8 mmol) was added dropwise. The mixture was stirred at -78° for 15 min then warmed to RT for 30 min and quenched in sat. aqueous Na/K tartrate. This solution was extracted with EtOAc. The organic layer was washed with brine, dried (Na2SO4), and concentrated. Flash chromatography (silica 50% EtOAc/hexane) provided 4-2 as a brown oil. Rf 0.38 (silica, 50% EtOAc/hexane). quenched in sat. aqueous Na/K tartrate This solution was extracted with EtOAc The organic layer was washed with brine dried (Na2SO4) concentrated

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

Procedure: 2-Methylindole (1.7 g, 13 mmol) in 130 mL Et2O was treated with nBuLi (1.6M in hexane, 24.4 mL, 39 mmol) and KOtBu (1.0M in THF, 26 mL, 26 mmol) at RT for 40 min, then diethylcarbonate (3.15 mL, 26 mmol) was added. After 1 h the reaction was quenched with water, adjusted to pH 7 with 6N HCl, extracted with EtOAc, then the organic layer was washed with water and brine, dried (MgSO4), and concentrated. Flash chromatography (silica 10% then 20% EtOAc/hexane) provided 4-1 as a brown oil. Rf 0.33 (silica, 20% EtOAc/hexane). After 1 h the reaction was quenched with water extracted with EtOAc the organic layer was washed with water and brine dried (MgSO4) concentrated

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

Procedure: To a solution of ethyl 2-(1H-indol-2-yl)acetate (14.7 g, 72.2 mmol) in dichloromethane (150 mL) was added 4-dimethylaminopyridine (8.83 g, 72.2 mmol) and di-tert-butyl carbonate (23.7 g, 108 mmol) in portions. After stirring for 2 h at room temperature, the mixture was diluted with dichloromethane, washed with water, dried over magnesium sulfate and purified by silica gel chromatography (0 to 20% EtOAc in hexane) to give tert-butyl 2-((ethoxycarbonyl)methyl)-1H-indole-1-carboxylate (20.0 g, 91%). washed with water dried over magnesium sulfate purified by silica gel chromatography (0 to 20% EtOAc in hexane)

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

Procedure: To a solution of ethyl 2-(1H-indol-2-yl)acetate (14.7 g, 72.2 mmol) in dichloromethane (150 mL) was added 4-dimethylaminopyridine (8.83 g, 72.2 mmol) and di-tert-butyl carbonate (23.7 g, 108 mmol) in portions. After stirring for 2 h at room temperature, the mixture was diluted with dichloromethane, washed with water, dried over magnesium sulfate and purified by silica gel chromatography (0 to 20% EtOAc in hexane) to give tert-butyl 2-((ethoxycarbonyl)methyl)-1H-indole-1-carboxylate (20.0 g, 91%). washed with water dried over magnesium sulfate purified by silica gel chromatography (0 to 20% EtOAc in hexane)

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

Procedure: To a solution of ethyl 2-(1H-indol-2-yl)acetate (14.7 g, 72.2 mmol) in dichloromethane (150 mL) was added 4-dimethylaminopyridine (8.83 g, 72.2 mmol) and di-tert-butyl carbonate (23.7 g, 108 mmol) in portions. After stirring for 2 h at room temperature, the mixture was diluted with dichloromethane, washed with water, dried over magnesium sulfate and purified by silica gel chromatography (0 to 20% EtOAc in hexane) to give tert-butyl 2-((ethoxycarbonyl)methyl)-1H-indole-1-carboxylate (20.0 g, 91%). washed with water dried over magnesium sulfate purified by silica gel chromatography (0 to 20% EtOAc in hexane)

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

Procedure: A sample of 12.0 gm (0.048M) of ethyl-γ-2-nitrophenylacetoacetate was dissolved in 200 cc. glacial acetic acid. Approximately 21/2 spatulas of 5% Pd/C was added to the solution and the compound was reduced on the Parr hydrogenator. Ethyl-2-indolylacetate was obtained as a dark orangy oily liquid after removal of catalyst and solvent.

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

Procedure: Ester 4-1 (0.54 g, 2.6 mmol) was dissolved in 13 mL CH2Cl2 at -78°, and DIBAL (1M in CH2Cl2, 5.8 ml, 5.8 mmol) was added dropwise. The mixture was stirred at -78° for 15 min then warmed to RT for 30 min and quenched in sat. aqueous Na/K tartrate. This solution was extracted with EtOAc. The organic layer was washed with brine, dried (Na2SO4), and concentrated. Flash chromatography (silica 50% EtOAc/hexane) provided 4-2 as a brown oil. quenched in sat. aqueous Na/K tartrate This solution was extracted with EtOAc The organic layer was washed with brine dried (Na2SO4) concentrated

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

Procedure: Ester 4-1 (0.54 g, 2.6 mmol) was dissolved in 13 mL CH2Cl2 at -78°, and DIBAL (1M in CH2Cl2, 5.8 ml, 5.8 mmol) was added dropwise. The mixture was stirred at -78° for 15 min then warmed to RT for 30 min and quenched in sat. aqueous Na/K tartrate. This solution was extracted with EtOAc. The organic layer was washed with brine, dried (Na2SO4), and concentrated. Flash chromatography (silica 50% EtOAc/hexane) provided 4-2 as a brown oil. Rf 0.38 (silica, 50% EtOAc/hexane). quenched in sat. aqueous Na/K tartrate This solution was extracted with EtOAc The organic layer was washed with brine dried (Na2SO4) concentrated