ethyl furan-3-carboxylate

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

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

Procedure: 3-Furancarboxylic acid ethyl ester (1.4 g, 10.0 mmol) was dissolved in acetic acid (10 mL), bromine (1.6 g, 10.0 mmol) was added, and the mixture was stirred overnight. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20). The obtained crude fraction was dissolved in N,N-dimethylformamide (15 mL), palladium acetate (0.18 g, 0.78 mmol), triphenylphosphine (0.41 g, 1.55 mmol), triethylamine (2.2 mL, 15.5 mmol), and water (0.7 mL, 38.8 mmol) were added, and the mixture was stirred at 80° C. overnight under a carbon monoxide atmosphere. 1N Hydrochloric acid was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was purified by high performance liquid chromatography to give the title compound (0.47 g). The solvent was evaporated under reduced pressure the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20) The obtained crude fraction the mixture was stirred at 80° C. overnight under a carbon monoxide atmosphere the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous sodium sulfate concentrated under reduced pressure The obtained residue was purified by high performance liquid chromatography

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

Procedure: To a stirred solution of 2.8 g (0.12 mole) of sodium in 200 ml of ethanol was added 13.3 g (0.10 mole) of 2-oxindole, followed by 16.8 g of ethyl 3-furoate. The mixture was heated under reflux for 47 hours, cooled and then the solvent was removed by evaporation in vacuo. The residue was triturated under 200 ml of ether, and the solid was collected by filtration and discarded. The filtrate was evaporated in vacuo, and the residue triturated under isopropyl alcohol and recovered by filtration. The solid was suspended in 250 ml of water, which was then acidified with concentrated hydrochloric acid. This mixture was stirred to give a solid, which was recovered by filtration. This latter solid was recrystallized from acetic acid followed by acetonitrile to give 705 mg of the title compound, mp 185°-186° C. The mixture was heated under reflux for 47 hours cooled the solvent was removed by evaporation in vacuo The residue was triturated under 200 ml of ether the solid was collected by filtration The filtrate was evaporated in vacuo the residue triturated under isopropyl alcohol recovered by filtration to give a solid, which was recovered by filtration This latter solid was recrystallized from acetic acid

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

Procedure: To a stirred solution of 2.8 g (0.12 mole) of sodium in 200 ml of ethanol was added 13.3 g (0.10 mole) of 2-oxindole, followed by 16.8 g of ethyl 3-furoate. The mixture was heated under reflux for 47 hours, cooled and then the solvent was removed by evaporation in vacuo. The residue was triturated under 200 ml of ether, and the solid was collected by filtration and discarded. The filtrate was evaporated in vacuo, and the residue triturated under diisopropyl ether and recovered by filtration. The solid was suspended in 250 ml of water, which was then acidified with concentrated hydrochloric acid. This mixture was stirred to give a solid, which was recovered by filtration. This latter solid was recrystallized from acetic acid followed by acetonitrile to give 705 mg of the title compound, mp 185°-186° C. The mixture was heated under reflux for 47 hours cooled the solvent was removed by evaporation in vacuo The residue was triturated under 200 ml of ether the solid was collected by filtration The filtrate was evaporated in vacuo the residue triturated under diisopropyl ether recovered by filtration to give a solid, which was recovered by filtration This latter solid was recrystallized from acetic acid

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

Procedure: To 300 ml of THF was added with cooling (ice-bath) 300 ml (0.3 mol) of 1M TiCl4 in methylene chloride and the mixture was stirred for 10 min. To the above mixture was added at room temperature 90.5 ml (0.6 mol) of TMEDA, the mixture was stirred for 10 min, and then, 44.12 g (0.675 mol) of Zn dust was added with cooling to maintain the mixture at room temperature and stirred for 40 min. To the resulting reaction mixture was added dropwise a mixture of ethyl 3-furoate (10.5 g, 0.075 mol), 31 g (0.165 mol) of dibromoethane in 200 ml of THF, and the mixture was stirred at room temperature for 2.5 h. After adding 90 ml of aqueous potassium carbonate solution, the mixture was concentrated in vacuo, the residue was diluted with 20 g of basic alumina, passed through basic alumina column (ether/TEA 200:1), and the eluent was concentrated. The residue was triturated in ether (200 ml), filtered, and the filtrate was distilled (80°-95° C./25 mm) to afford 6.2 g of (54.3%) of 1-(3-furyl)-1-ethoxy-2-methylethylene (Formula III: R2 =CH3 ;R3 =H; R4 =CH3CH2O;R5 =3-Furyl; and Formula III: R2 =H;R3 =CH3 ;R4 =3-Furyl; R5 =CH3CH2O). the mixture was stirred for 10 min with cooling stirred for 40 min To the resulting reaction mixture was added dropwise the mixture was stirred at room temperature for 2.5 h the mixture was concentrated in vacuo the residue was diluted with 20 g of basic alumina the eluent was concentrated The residue was triturated in ether (200 ml) filtered the filtrate was distilled (80°-95° C./25 mm)

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

Procedure: To 300 ml of THF was added with cooling (ice-bath) 300 ml (0.3 mol) of 1M TiCl4 in methylene chloride and the mixture was stirred for 10 min. To the above mixture was added at room temperature 90.5 ml (0.6 mol) of TMEDA, the mixture was stirred for 10 min, and then, 44.12 g (0.675 mol) of Zn dust was added with cooling to maintain the mixture at room temperature and stirred for 40 min. To the resulting reaction mixture was added dropwise a mixture of ethyl 3-furoate (10.5 g, 0.075 mol), 31 g (0.165 mol) of dibromoethane in 200 ml of THF, and the mixture was stirred at room temperature for 2.5 h. After adding 90 ml of aqueous potassium carbonate solution, the mixture was concentrated in vacuo, the residue was diluted with 20 g of basic alumina, passed through basic alumina column (ether/TEA 200:1), and the eluent was concentrated. The residue was triturated in ether (200 ml), filtered, and the filtrate was distilled (80°-95° C./25 mm) to afford 6.2 g of (54.3%) of 1-(3-furyl)-1-ethoxy-2-methylethylene (Formula III: R2 =CH3 ;R3 =H; R4 =CH3CH2O;R5 =3-Furyl; and Formula III: R2 =H;R3 =CH3 ;R4 =3-Furyl; R5 =CH3CH2O). the mixture was stirred for 10 min with cooling stirred for 40 min To the resulting reaction mixture was added dropwise the mixture was stirred at room temperature for 2.5 h the mixture was concentrated in vacuo the residue was diluted with 20 g of basic alumina the eluent was concentrated The residue was triturated in ether (200 ml) filtered the filtrate was distilled (80°-95° C./25 mm)

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

Procedure: To 300 mL of THF was added with cooling (ice-bath) 300 mL (0.3 mol) of 1M TiCl4 in methylene chloride and the mixture was stirred for 10 min. To the above mixture was added at room temperature 90.5 mL (0.6 mol) of TMEDA, the mixture was stirred for 10 min, and then 44.12 g (0.675 mol) of Zn dust was added with cooling to maintain the mixture at room temperature and stirred for 40 min. To the resulting reaction mixture was added dropwise to a mixture of ethyl 3-furoate (10.5 g, 0.075 mol), 31 g (0.165 mol) of dibromoethane in 200 mL of THF, and the mixture was stirred at room temperature for 2.5 h. After adding 90 mL of aqueous potassium carbonate solution, the mixture was concentrated in vacuo, the residue was diluted with 20 g of basic alumina, passed through a basic alumina column (ether/TEA 200:1), and the eluent was concentrated. The residue was triturated in ether (200 mL), filtered, and the filtrate was distilled (80°-95° C./25 mm) to afford 6.2 g (54.3%) of 1-(3-furyl)-1-ethoxy-2-methylethylene (Formula III: R3 =CH3 ; R4 =H; R6 =CH3CH2O; R5 =3-Furyl; and Formula III: R3 =H; R4 =CH3 ; R6 =3-Furyl; R5 =CH3H2O). the mixture was stirred for 10 min with cooling stirred for 40 min To the resulting reaction mixture the mixture was stirred at room temperature for 2.5 h the mixture was concentrated in vacuo the residue was diluted with 20 g of basic alumina the eluent was concentrated The residue was triturated in ether (200 mL) filtered the filtrate was distilled (80°-95° C./25 mm)

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

Procedure: To a stirred solution of 2.8 g (0.12 mole) of sodium in 200 ml of ethanol was added 13.3 g (0.10 mole) of 2-oxindole, followed by 16.8 g of ethyl 3-furoate. The mixture was heated under reflux for 47 hours, cooled and then the solvent was removed by evaporation in vacuo. The residue was triturated under 200 ml of ether, and the solid was collected by filtration and discarded. The filtrate was evaporated in vacuo, and the residue triturated under isopropyl alcohol and recovered by filtration. The solid was suspended in 250 ml of water, which was then acidified with concentrated hydrochloric acid. This mixture was stirred to give a solid, which was recovered by filtration. This latter solid was recrystallized from acetic acid followed by acetonitrile to give 705 mg of the title compound, m.p. 185°-186° C. The mixture was heated under reflux for 47 hours cooled the solvent was removed by evaporation in vacuo The residue was triturated under 200 ml of ether the solid was collected by filtration The filtrate was evaporated in vacuo the residue triturated under isopropyl alcohol recovered by filtration to give a solid, which was recovered by filtration This latter solid was recrystallized from acetic acid

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a nitrogen-purged, 300-mL, three-neck, round-bottom flask equipped with a thermocouple/thermowell, addition funnel, distillation head, and magnetic stirrer was charged 75 mL of toluene and 26.71 g (0.100 mole) of distilled ethyl 3-bromo-2-ethoxytetrahydro-3-furoate and 42 mL (0.11 mole) of 21 % alcoholic sodium ethoxide. The mixture was heated to 50° C. while following the course of reaction by GC. An additional 17 mL (0.046 mole) of sodium ethoxide solution was needed to complete the reaction. The pressure of the system was lowered to about 210 mm to distill the ethanol/toluene azeotrope. When most of the ethanol was removed the mixture was cooled to room temperature and 50 mL of 5% hydrochloric acid was added. The layers were separated and the aqueous layer was extracted once with 25 mL of toluene. The two organic layers were combined and washed with 50 mL of 5% aqueous sodium bicarbonate and 50 mL of saturated sodium bicarbonate. The solution was dried over anhydrous magnesium sulfate and decolorizing carbon then filtered. Solvent was removed from the filtrate by distillation through a 1 0-inch Vigreux column at atmospheric pressure. The resulting ethyl 3-furoate weighed 11.25 g. Analysis by GC showed 90.4 area% ethyl 3-furoate and 9.6 area% toluene. The assay-yield of ethyl 3-furoate was 10.2 g (72.6% of theory). The identity of the product was confirmed by NMR and mass spectrometry. To a nitrogen-purged 300-mL, three-neck, round-bottom flask equipped with a thermocouple/thermowell, addition funnel distillation head, and magnetic stirrer the course of reaction by GC the reaction to distill the ethanol/toluene azeotrope When most of the ethanol was removed the mixture was cooled to room temperature 50 mL of 5% hydrochloric acid was added The layers were separated the aqueous layer was extracted once with 25 mL of toluene washed with 50 mL of 5% aqueous sodium bicarbonate and 50 mL of saturated sodium bicarbonate The solution was dried over anhydrous magnesium sulfate then filtered Solvent was removed from the filtrate by distillation through a 1 0-inch Vigreux column at atmospheric pressure

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

Procedure: To a stirred solution of 2.8 g (0.12 mole) of sodium in 200 ml of ethanol was added 13.3 g (0.10 mole) of 2-oxindole, followed by 16.8 g of ethyl 3-furoate. The mixture was heated under reflux for 47 hours, cooled and then the solvent was removed by evaporation in vacuo. The residue was triturated under 200 ml of ether, and the solid was collected by filtration and discarded. The filtrate was evaporated in vacuo, and the residue triturated under ispropyl alcohol and recovered by filtration. The solid was suspended in 250 ml of water, which was then acidified with concentrated hydrochloric acid. This mixture was stirred to give a solid, which was recovered by filtration. This latter solid was recrystallized from acetic acid followed by acetonitrile to give 705 mg of the title compound, m.p. 185°-186° C. The mixture was heated under reflux for 47 hours cooled the solvent was removed by evaporation in vacuo The residue was triturated under 200 ml of ether the solid was collected by filtration The filtrate was evaporated in vacuo the residue triturated under ispropyl alcohol recovered by filtration to give a solid, which was recovered by filtration This latter solid was recrystallized from acetic acid

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

Procedure: To a stirred solution of 2.8 g (0.12 mole) of sodium in 200 ml of ethanol was added 13.3 g (0.10 mole) of 2-oxindole, followed by 16.8 g of ethyl 3-furoate. The mixture was heated under reflux for 47 hours, cooled and then the solvent was removed by evaporation in vacuo. The residue was triturated under 200 ml of ether, and the solid was collected by filtration and discarded. The filtrate was evaporated in vacuo, and the residue triturated under ispropyl alcohol and recovered by filtration. The solid was suspended in 250 ml of water, which was then acidified with concentrated hydrochloric acid. This mixture was stirred to give a solid, which was recovered by filtration. This latter solid was recrystallized from acetic acid followed by acetonitrile to give 705 mg of the title compound, m.p. 185°-186° C. The mixture was heated under reflux for 47 hours cooled the solvent was removed by evaporation in vacuo The residue was triturated under 200 ml of ether the solid was collected by filtration The filtrate was evaporated in vacuo the residue triturated under ispropyl alcohol recovered by filtration to give a solid, which was recovered by filtration This latter solid was recrystallized from acetic acid

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

Procedure: To a stirred solution of 2.8 g (0.12 mole) of sodium in 200 ml of ethanol was added 13.3 g (0.10 mole) of 2-oxindole, followed by 16.8 g of ethyl 3furoate. The mixture was heated under reflux for 47 hours, cooled and then the solvent was removed by evaporation in vacuo. The residue was triturated under 200 ml of ether, and the solid was collected by filtration and discarded. The filtrate was evaporated in vacuo, and the residue triturated under diisopropyl ether and recovered by filtration. The solid was suspended in 250 ml of water, which was then acidified with concentrated hydrochloric acid. This mixture was stirred to give a solid, which was recovered by filtration. This latter solid was recrystallized from acetic acid followed by acetonitrile to give 705 mg of the title compound, mp 185°-186° C. The mixture was heated under reflux for 47 hours cooled the solvent was removed by evaporation in vacuo The residue was triturated under 200 ml of ether the solid was collected by filtration The filtrate was evaporated in vacuo the residue triturated under diisopropyl ether recovered by filtration to give a solid, which was recovered by filtration This latter solid was recrystallized from acetic acid