diethyl butanedioate

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

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

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

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

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

Procedure: 14.57 g of Na was added portionwise to 400 ml of EtOH. To the mixture was added a solution of 38.91 g of 1-cyclopropyl-1H-pyrrole-2-carbaldehyde and 48.23 ml of diethyl succinate in 100 ml of EtOH at 50° C., then the mixture was refluxed overnight. 140 ml of 5N HCl was added to the mixture at 0° C. and EtOH was evaporated. The concentrate was extracted with CHCl3 and the extract was dried over Na2SO4 and concentrated to give red oil. The material was dissolved in 400 ml of acetic anhydride and 47.40 g of AcOK was added thereto. The mixture was refluxed for 30 min and allowed to cool to room temperature. The mixture was filtrated and the filtrate was concentrated. The residue was purified on SiO2 column chromatography (n-hexane-EtOAc system) to give 72.3 g of ethyl 4-acetoxy-1-cyclopropyl-1H-indole-6-carboxylate as red oil. the mixture was refluxed overnight EtOH was evaporated The concentrate was extracted with CHCl3 the extract was dried over Na2SO4 concentrated to give red oil The mixture was refluxed for 30 min The mixture was filtrated the filtrate was concentrated The residue was purified on SiO2 column chromatography (n-hexane-EtOAc system)

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

Procedure: To a 250 mL round bottom flask were added 2-methoxybenzaldehyde (2.0 g, 14.7 mmol), diethyl butanedioate (6.4 g, 36.7 mmol) and t-BuOH (35 mL). KO-t-Bu (3.3 g, 29.4 mmol) was added in portions. The reaction mixture was stirred at room temperature for 2 hours and then diluted with 0.5 N HCl (120 mL) and extracted with EtOAc. The organic layer was back extracted with 5% KOH (60 mL). Aqueous layer was acidified with 1N HCl and extracted with EtOAc. Organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product was treated with Ac2O (9.7 mL, 103 mmol) and NaOAc (2.05 g, 25 mmol) at 120° C. under nitrogen overnight. The reaction mixture was cooled with an ice bath and diluted with 150 mL of water. The aqueous solution was carefully removed by slow decantation. The remaining residue was dissolved in EtOAc (30 mL), dried over sodium sulfate, filtered and concentrated. The crude product was purified on a silica gel column eluting with a gradient of 100% hexanes to 25% EtOAc/hexanes to give the title intermediate (0.52 g) as a light yellow solid. extracted with EtOAc The organic layer was back extracted with 5% KOH (60 mL) extracted with EtOAc Organic layer was washed with brine dried over sodium sulfate filtered concentrated The reaction mixture was cooled with an ice bath The aqueous solution was carefully removed by slow decantation The remaining residue was dissolved in EtOAc (30 mL) dried over sodium sulfate filtered concentrated The crude product was purified on a silica gel column eluting with a gradient of 100% hexanes to 25% EtOAc/hexanes

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

Procedure: Potassium t-butoxide, 24.7 g (0.35M), was dissolved in 200 ml of refluxing t-butanol. A mixture of isobutyraldehyde, 18.2 ml (0.20M) and diethyl succinate 41.55 ml (0.25M) was added to the t-butanol solution over 30 min. The reaction mixture was stirred under reflux, for 2 h. The solvent was removed from the reaction mixture by evaporation under reduced pressure and acidified with 2N HCl. The product was extracted with ethyl ether, Et2O (3×200 ml). The ether solution was washed with water (3×200 ml); and the product was extracted with 10% Na2CO3 (4×200 ml). The solution was acidified with conc. HCl solution and the product was isolated by extraction with Et2O (4×150 ml). The ether layer was washed with water, dried over sodium sulfate, and evaporated. The remaining oil was dissolved in ethanol (300 ml) and hydrogenated in the presence of 10% palladium on charcoal (3.0 g). The resultant mixture was filtered through Celite and the solvent was evaporated to yield 38.04 g 2-carboethoxycarbonyl-4-methyl pentanoic acid as a mixture of isomers in the form of an oil. The isolated monoethyl ester was further purified on silica gel by flash chromatography using as eluent mixture ethyl acetate:hexane:acetic acid (1:10:0.05, v/v). under reflux, for 2 h The solvent was removed from the reaction mixture by evaporation under reduced pressure The product was extracted with ethyl ether, Et2O (3×200 ml) The ether solution was washed with water (3×200 ml) and the product was extracted with 10% Na2CO3 (4×200 ml) the product was isolated by extraction with Et2O (4×150 ml) The ether layer was washed with water dried over sodium sulfate evaporated The remaining oil was dissolved in ethanol (300 ml) and hydrogenated in the presence of 10% palladium on charcoal (3.0 g) The resultant mixture was filtered through Celite the solvent was evaporated

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

Procedure: Potassium t-butoxide, 24.7 g (0.35M), was dissolved in 200 ml of refluxing t-butanol. A mixture of isobutyraldehyde, 18.2 ml (0.20M) and diethyl succinate 41.55 ml (0.25M) was added to the t-butanol solution over 30 min. The reaction mixture was stirred under reflux, for 2 h. The solvent was removed from the reaction mixture by evaporation under reduced pressure and acidified with 2N HCl. The product was extracted with ethyl ether, Et2O (3×200 ml). The ether solution was washed with water (3×200 ml); and the product was extracted with 10% Na2CO3 (4×200 ml). The solution was acidified with conc. HCl solution and the product was isolated by extraction with Et2O (4×150 ml). The ether layer was washed with water, dried over sodium sulfate, and evaporated. The remaining oil was dissolved in ethanol (300 ml) and hydrogenated in the presence of 10% palladium on charcoal (3.0 g). The resultant mixture was filtered through Celite and the solvent was evaporated to yield 38.04 g 2-carboethoxycarbonyl-4-methyl pentanoic acid as a mixture of isomers in the form of an oil. The isolated monoethyl ester was further purified on silica gel by flash chromatography using as eluent mixture ethyl acetate:hexane:acetic acid (1:10:0.05, v/v). under reflux, for 2 h The solvent was removed from the reaction mixture by evaporation under reduced pressure The product was extracted with ethyl ether, Et2O (3×200 ml) The ether solution was washed with water (3×200 ml) and the product was extracted with 10% Na2CO3 (4×200 ml) the product was isolated by extraction with Et2O (4×150 ml) The ether layer was washed with water dried over sodium sulfate evaporated The remaining oil was dissolved in ethanol (300 ml) and hydrogenated in the presence of 10% palladium on charcoal (3.0 g) The resultant mixture was filtered through Celite the solvent was evaporated

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

Procedure: Dissolving 19.14 g of metal sodium in 400 ml of ethanol, 110.8 ml of diethyl succinate and 100 g of piperonal were added, and the solution was heated and refluxed for 3 hours. The reaction solution was concentrated in vacuo, and the residue was dissolved in 700 ml of water, and washed with 300 ml of diethyl ether. The water layer was stirred in ice, adjusted to pH 1 by concentrated hydrochloric acid, and extracted with 300 ml of diethyl ether. The diethyl ether layer was washed once with saturated brine, and dried over magnesium sulfate anhydride, and concentrated in vacuo. The obtained oily residue was dissolved by 181.4 g in 350 ml of ethanol, and 400 ml of 5N sodium hydroxide was added to stir overnight at room temperature. The reaction solution was concentrated in vacuo, and the residue was washed with 200 ml of diethyl ether. The water layer was stirred in ice, adjusted to pH 1 by concentrated hydrochloric acid, and extracted with 400 ml of ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over magnesium sulfate anhydride, and concentrated in vacuo. To the obtained residue, 300 ml of diethyl ether was added to solidify, and the captioned compound was obtained. Yield: 67.34 g. were added the solution was heated refluxed for 3 hours The reaction solution was concentrated in vacuo the residue was dissolved in 700 ml of water washed with 300 ml of diethyl ether extracted with 300 ml of diethyl ether The diethyl ether layer was washed once with saturated brine dried over magnesium sulfate anhydride concentrated in vacuo The obtained oily residue was dissolved by 181.4 g in 350 ml of ethanol 400 ml of 5N sodium hydroxide was added to stir overnight at room temperature The reaction solution was concentrated in vacuo the residue was washed with 200 ml of diethyl ether The water layer was stirred in ice extracted with 400 ml of ethyl acetate The ethyl acetate layer was washed with saturated brine dried over magnesium sulfate anhydride concentrated in vacuo To the obtained residue, 300 ml of diethyl ether was added the captioned compound was obtained

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethanol (20 cm3) was added portionwise to a suspension of finely divided sodium (10.0 g) in dry toluene (100 cm3). On completion of the addition the mixture was heated for 3.5 hours at 80° C. To the resulting yellow suspension, cooled to 20° C., was added dropwise, over a period of 1 hour, a mixture of diethyl succinate (70.0 g) and ethyl formate (35.0 g), whilst the temperature of the mixture was maintained in the range 20° to 30° C. The mixture was kept at the ambient temperature for 16 hours after which water (100 cm3) was added carefully. On completion of the addition the mixture To the resulting yellow suspension, cooled to 20° C. was added dropwise, over a period of 1 hour whilst the temperature of the mixture was maintained in the range 20° to 30° C

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethanol (20 cm3) was added portionwise to a suspension of finely divided sodium (10.0 g) in dry toluene (100 cm3). On completion of the addition the mixture was heated for 3.5 hours at 80° C. To the resulting yellow suspension, cooled to 20° C., was added dropwise, over a period of 1 hour, a mixture of diethyl succinate (70.0 g) and ethyl formate (35.0 g), whilst the temperature of the mixture was maintained in the range 20° to 30° C. The mixture was kept at the ambient temperature for 16 hours after which water (100 cm3) was added carefully. On completion of the addition the mixture To the resulting yellow suspension, cooled to 20° C. was added dropwise, over a period of 1 hour whilst the temperature of the mixture was maintained in the range 20° to 30° C

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred mixture of 17.4 g of diethyl succinate, 19.6 g of 3,4,5-trimethoxybenzaldehyde in 175 ml of ethanol chilled to 0° C. under argon was added 5.0 g of sodium hydride (60% in oil) in three equal portions. The solution was then refluxed for 30 minutes and 125 ml of 2N sodium hydroxide added. The solution was refluxed for 2 hours and concentrated under vacuum. The residue was diluted with water, extracted with ether and the aqueous layer acidified with concentrated hydrochloric acid. The mixture was extracted three times with 45 ml of ether and the ether extracts washed with saturated sodium chloride solution. The ether layer was dried (MgSO4) and the solvent removed under vacuum to give 24.82 g of [(3,4,5-trimethoxyphenyl)methylene]butanedioic acid as a yellow oil. The solution was then refluxed for 30 minutes The solution was refluxed for 2 hours concentrated under vacuum The residue was diluted with water extracted with ether The mixture was extracted three times with 45 ml of ether the ether extracts washed with saturated sodium chloride solution The ether layer was dried (MgSO4) the solvent removed under vacuum