ethyl furan-2-carboxylate

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:80.01; 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: A solution of 60 g. of 3,4-methylenedioxybenzyl bromide in 200 ml. of carbon disulfide was slowly added over a period of 45 minutes to a solution of 260 g. of ethyl 2-furoate and 20 g. of zinc chloride in 600 ml. of carbon disulfide held at 31 10° C. The reaction mixture was allowed to warm to room temperature, filtered, extracted with water and saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The solvent was removed and the residue distilled to give 27 g. of ethyl 5-(3,4-methylenedioxybenzyl)-2-furoate, b.p. 162°-166° C. (0.5 mm), which crystallized to a solid, m.p. 67°-68° C. held at 31 10° C filtered extracted with water and saturated sodium chloride solution dried over anhydrous sodium sulfate The solvent was removed the residue distilled to give 27 g of ethyl 5-(3,4-methylenedioxybenzyl)-2-furoate, b.p. 162°-166° C. (0.5 mm), which crystallized to a solid, m.p. 67°-68° C.

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

Procedure: In a nitrogen atmosphere, lithium bis (trimethylsilyl) amide (100 mL, 100 mmol) was added dropwise into a solution of 4-picoline (4.6 g, 49.4 mmol) and ethyl 2-furancarboxylate (7.7 g, 54.9 mmol) in tetrahydrofuran (40 mL) at 0° C. over 1 hour, followed by stirring as it was for 2 hours. Hexane (140 mL) was added to the reaction solution, and the resulting crystals were collected by filtration. The resulting crystals were dissolved in ethyl acetate and an aqueous saturated solution of ammonium chloride. The organic layer was washed with an aqueous saturated solution of ammonium chloride (×2) and brine, dried over anhydrous sodium sulfate, and concentrated. Hexane was added to the residue, and the resulting precipitates were collected by filtration and washed with hexane, to give the title compound (6.5 g, 70%) as a pale yellow solid. the resulting crystals were collected by filtration The resulting crystals were dissolved in ethyl acetate The organic layer was washed with an aqueous saturated solution of ammonium chloride (×2) and brine dried over anhydrous sodium sulfate concentrated Hexane was added to the residue the resulting precipitates were collected by filtration washed with hexane

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

Procedure: In a manner similar to that in Reference Example 13, by using 4-methylpyridine in place of 3,4-dimethylpyridine and using ethyl 3-(4-pyridyl)furan-2-carboxylate (133 mg, 0.612 mmol) obtained in Step 1, in place of ethyl furan-2-carboxylate, the entitled Compound ad (35.3 mg, 18%) was obtained.

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

Procedure: 3,4-Dimethylpyridine (2.25 mL, 20.0 mmol) and ethyl furan-2-carboxylate (5.02 mL, 40.0 mmol) were dissolved in THF (20 mL), and at 0° C., a 1.0 mol/L solution of lithium hexamethyldisilazide in THF (40.0 mL, 40.0 mmol) was added dropwise thereto, followed by stirring at room temperature for 1.5 hours. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The organic layer was washed successively with a saturated aqueous solution of ammonium chloride and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane:ethyl acetate=1:2) to afford 1-(2-furyl)-2-(3-methylpyridin-4-yl)ethanone (3.34 g, 16.6 mmol). followed by extraction with ethyl acetate The organic layer was washed successively with a saturated aqueous solution of ammonium chloride a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate the solvent was distilled away under reduced pressure The resulting residue was purified through silica gel column chromatography (hexane:ethyl acetate=1:2)

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

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

Procedure: To an ice cold suspension of 0.92 g (23 mmol) of sodium hydride (NaH 60% dispersion in mineral oil) (previously washed with hexane and dried under vacuum) in 25 mL of 1,2-dimethoxyethane (DME) was added 0.9 g (5.76 mmol) of methyl cyclohexylacetate, and the resulting mixture was stirred at 0° C. for 20 min. Then 1.2 g (8.56 mmol) of ethyl 2-furoate was added, and the reaction mixture was heated at reflux overnight. The mixture was then cooled to 0° C., quenched by the addition of 1 M HCl solution to pH=3, and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated to give a brown oil which was chromatographed on silica gel (Biotage; 10% hexane in dichloromethane) to afford 1.1 g (76% yield) of desired 2-cyclohexyl-3-furan-2-yl-3-oxo-propionic acid methyl ester as indicated by 1H NMR. previously washed with hexane dried under vacuum) in 25 mL of 1,2-dimethoxyethane (DME) the reaction mixture was heated at reflux overnight The mixture was then cooled to 0° C. quenched by the addition of 1 M HCl solution to pH=3 extracted with ethyl acetate The combined organic extracts were washed with brine dried over sodium sulfate concentrated to give a brown oil which was chromatographed on silica gel (Biotage; 10% hexane in dichloromethane)

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

Procedure: To an ice cold suspension of 0.92 g (23 mmol) of sodium hydride (NaH 60% dispersion in mineral oil) (previously washed with hexane and dried under vacuum) in 25 mL of 1,2-dimethoxyethane (DME) was added 0.9 g (5.76 mmol) of methyl cyclohexylacetate, and the resulting mixture was stirred at 0° C. for 20 min. Then 1.2 g (8.56 mmol) of ethyl 2-furoate was added, and the reaction mixture was heated at reflux overnight. The mixture was then cooled to 0° C., quenched by the addition of 1 M HCl solution to pH=3, and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated to give a brown oil which was chromatographed on silica gel (Biotage; 10% hexane in dichloromethane) to afford 1.1 g (76% yield) of desired 2-cyclohexyl-3-furan-2-yl-3-oxo-propionic acid methyl ester as indicated by 1H NMR. previously washed with hexane dried under vacuum) in 25 mL of 1,2-dimethoxyethane (DME) the reaction mixture was heated at reflux overnight The mixture was then cooled to 0° C. quenched by the addition of 1 M HCl solution to pH=3 extracted with ethyl acetate The combined organic extracts were washed with brine dried over sodium sulfate concentrated to give a brown oil which was chromatographed on silica gel (Biotage; 10% hexane in dichloromethane)