ethyl 3-(furan-2-yl)-3-oxopropanoate

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: To a solution of ethyl 3-(2-furyl)-3-ketopropionate (2.45 g, 13.4 mmol) in 20 mL of absolute ethanol was added sodium ethoxide (4.6 mL of a 21% weight solution in ethanol, 12.2 mmol) followed by 2,2,2-trifluoroacetoyl bromide-N-(4-methoxyphenyl)hydrazone (1.82 g, 6.1 mmol). This mixture was stirred at ambient temperature for 4 h. The volatiles were removed in vacuo and the residue was dissolved in ethyl acetate, washed with water and brine, dried (MgSO4) and concentrated. The residue was purified by recrystallization from hexane/ethyl acetate to afford 1.4 g (61%) of the title compound. LRMS (ES+): 381.2 (M+H)+. The volatiles were removed in vacuo the residue was dissolved in ethyl acetate washed with water and brine dried (MgSO4) concentrated The residue was purified by recrystallization from hexane/ethyl acetate

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

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

Procedure: To a solution of ethyl 3-(2-furyl)-3-ketopropionate (2.1 g, 11.5 mmol) in 20 mL of benzene was added dimethylformamide dimethylacetal (2.3 mL, 17.3 mmol). The resulting solution was stirred at 80° C. for 2 h. The reaction was cooled, filtered through a pad of silica gel and concentrated in vacuo. A portion of the residue (0.60 g, 2.54 mmol) was dissolved in 20 mL of glacial acetic acid and then there was added 4-fluoro-3-cyanophenylhydrazine tin chloride (1.05 g, 2.8 mmol). The reaction mixture was stirred at 100° C. for 4 h. The reaction was allowed to cool to room temperature and the acetic acid was removed in vacuo. The residue was diluted with ethyl acetate and the organics were washed with saturated aq NaHCO3 and brine, dried (MgSO4) and concentrated. The residue was purified by flash chromatography (elution with gradient of 6:1→3:1 hexanes/ethyl acetate) to afford 0.32 g (39%) of the title compound. LRMS (ES+): 326.2 (M+H)+. The reaction was cooled filtered through a pad of silica gel concentrated in vacuo The reaction mixture was stirred at 100° C. for 4 h to cool to room temperature the acetic acid was removed in vacuo The residue was diluted with ethyl acetate the organics were washed with saturated aq NaHCO3 and brine dried (MgSO4) concentrated The residue was purified by flash chromatography (elution with gradient of 6:1→3:1 hexanes/ethyl acetate)

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

Procedure: Sodium hydride (4.4 grams) and 10.7 grams of diethyl carbonate are suspended in 60 ml of tetrahydrofuran and 10 grams of 2-acetylfuran is gradually added thereto by keeping the inner temperature at 40°to 50° C. A small amount of ethanol is added thereto, heated to reflux for three hours, and the reaction is made stopped by addition of 20 ml of ethanol. The mixture is poured into ice water, extracted with ether, the ether extracts are combined, washed with water, dried with anhydrous magnesium sulfate, and ether is evaporated therefrom. The resulting oil is purified by distilling in vacuo to give 10 grams of pale yellow oily product, b.p. 90° C./3 mmHg. at 40°to 50° C heated to reflux for three hours extracted with ether washed with water dried with anhydrous magnesium sulfate, and ether is evaporated The resulting oil is purified by distilling in vacuo

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

Procedure: To a solution of ethyl 3-(2-furyl)-3-ketopropionate (2.1 g, 11.5 mmol) in 20 mL of benzene was added dimethylformamide dimethylacetal (2.3 mL, 17.3 mmol). The resulting solution was stirred at 80° C. for 2 h. The reaction was cooled, filtered through a pad of silica gel and concentrated in vacuo. A portion of the residue (0.60 g, 2.54 mmol) was dissolved in 20 mL of glacial acetic acid and then there was added 4-fluoro-3-cyanophenylhydrazine tin chloride (1.05 g, 2.8 mmol). The reaction mixture was stirred at 100° C. for 4 h. The reaction was allowed to cool to room temperature and the acetic acid was removed in vacuo. The residue was diluted with ethyl acetate and the organics were washed with saturated aq NaHCO3 and brine, dried (MgSO4) and concentrated. The residue was purified by flash chromatography (elution with gradient of 6:1→3:1 hexanes/ethyl acetate) to afford 0.32 g (39%) of the title compound. LRMS (ES+): 326.2 (M+H)+. The reaction was cooled filtered through a pad of silica gel concentrated in vacuo The reaction mixture was stirred at 100° C. for 4 h to cool to room temperature the acetic acid was removed in vacuo The residue was diluted with ethyl acetate the organics were washed with saturated aq NaHCO3 and brine dried (MgSO4) concentrated The residue was purified by flash chromatography (elution with gradient of 6:1→3:1 hexanes/ethyl acetate)

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

Procedure: Triethylamine (11.7 mL, 84.3 mmol) was added dropwise to a suspension of potassium ethyl malonate (13.4 g, 78.5 mmol) in acetonitrile (80 mL) at 10° C., followed by portionwise addition of anhydrous magnesium chloride (9.12 g, 95.8 mmol). The reaction mixture was warmed to room temperature and stirred for 2.5 h. The resulting white slurry was cooled to 0° C. and furan-2-carbonyl chloride (5.0 g, 38.3 mmol) in acetonitrile (20 mL) was added dropwise over a period of 20 min. The mixture was allowed to stir at ambient temperature overnight. The solvent was evaporated in vacuo and the residue was azeotroped with toluene (10 mL) then dissolved in toluene, cooled to between 0 and 5° C. and acidified with 13% aqueous hydrochloric acid (50 mL). After stirring for 15 min the aqueous phase was separated and the organic phase was washed with 13% aqueous hydrochloric acid (2×50 mL) followed by water (2×25 mL) and concentrated in vacuo to afford the crude compound. Purification by flash column chromatography over silica gel (100-200 mesh) using 5% ethyl acetate in petroleum ether as eluent afforded ethyl 3-(2-furyl)-3-oxo-propanoate (5.01 g, 72%) as a pale yellow liquid. The resulting white slurry was cooled to 0° C. to stir at ambient temperature overnight The solvent was evaporated in vacuo the residue was azeotroped with toluene (10 mL) then dissolved in toluene cooled to between 0 and 5° C. After stirring for 15 min the aqueous phase was separated the organic phase was washed with 13% aqueous hydrochloric acid (2×50 mL) concentrated in vacuo to afford the crude compound Purification by flash column chromatography over silica gel (100-200 mesh)

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

Procedure: To a solution of ethyl 3-(2-furyl)-3-ketopropionate (2.45 g, 13.4 mmol) in 20 mL of absolute ethanol was added sodium ethoxide (4.6 mL of a 21% weight solution in ethanol, 12.2 mmol) followed by 2, 2, 2-trifluoroacetoyl bromide -N-(4-methoxyphenyl)hydrazone (1.82 g, 6.1 mmol). This mixture was stirred at ambient temperature for 4 h. The volatiles were removed in vacuo and the residue was dissolved in ethyl acetate, washed with water and brine, dried (MgSO4) and concentrated. The residue was purified by recrystallization from hexane/ethyl acetate to afford 1.4 g (61%) of the title compound. LRMS (ES+): 381.2 (M+H)+. The volatiles were removed in vacuo the residue was dissolved in ethyl acetate washed with water and brine dried (MgSO4) concentrated The residue was purified by recrystallization from hexane/ethyl acetate

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

Procedure: To a solution of ethyl 3-(2-furyl)-3-ketopropionate (2.45 g, 13.4 mmol) in 20 mL of absolute ethanol was added sodium ethoxide (4.6 mL of a 21% weight solution in ethanol, 12.2 mmol) followed by 2,2,2-trifluoroacetoyl bromide-N-(4-methoxyphenyl)hydrazone (1.82 g, 6.1 mmol). This mixture was stirred at ambient temperature for 4 h. The volatiles were removed in vacuo and the residue was dissolved in ethyl acetate, washed with water and brine, dried (MgSO4) and concentrated. The residue was purified by recrystallization from hexane/ethyl acetate to afford 1.4 g (61%) of the title compound. LRMS (ES+): 381.2 (M+H)+. The volatiles were removed in vacuo the residue was dissolved in ethyl acetate washed with water and brine dried (MgSO4) concentrated The residue was purified by recrystallization from hexane/ethyl acetate