ethyl 5-formylfuran-2-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Formyl-2-furancarboxylic acid (2.9 g) was dissolved in N,N-dimethylformamide (30 ml), and potassium carbonate (2.9 g) and iodoethane (3.6 g) were added. The mixture was stirred at room temperature for 12 hours, poured into ice water and extracted with diethyl ether. The extract was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and the desired fractions were concentrated under reduced pressure to give 5-formyl- 2-furancarboxylic acid ethyl ester (1.3 g). 5-Formyl-2-furancarboxylic acid ethyl ester (1.3 g) in methylene chloride (5 ml) was slowly added dropwise to diethylaminosulfur trifluoride (DAST) (1.3 g) in methylene chloride (5 ml) at room temperature. The mixture was stirred at room temprature for 30 minutes, and water was added to the mixture. The resulting mixture was extracted with diethyl ether, and the extract was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and the desired fractions were concentrated under reduced pressure to give 5-difluoromethyl-2-furancarboxylic acid ethyl ester (0.7 g). 5-Difluoromethyl-2-furancarboxylic acid ethyl ester (2.3 g) synthesized in this manner was dissolved in ethanol (20 ml), and 1N aqueous sodium hydroxide (15 ml) was added. The mixture was stirred at room temperature and concentrated under reduced paressure. The residue was dissolved in water and washed with diethyl ether. The aqueous layer was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Precipitated crystals were collected by filtration and washed with hexane-isopropyl ether to give 5-difluoromethyl-2-furancarboxylic acid (1.2 g) as crystals. extracted with diethyl ether The extract was washed with water and saturated aqueous sodium chloride dried over anhydrous magnesium sulfate concentrated under reduced pressure the desired fractions were concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 24.2 g (0.056 mol) of isopropyltriphenylphosphonium iodide in 300 mL of THF at -20° C. was added 37.3 mL of a 1.5M solution of n-BuLi (0.056 mol) in hexane over a 20-min period. The dark brown solution was warmed to 0° C. and maintained at this temperature for 30 min, when almost all of the solid phosphonium salt had disappeared. A solution of 9.42 g (0.056 mol) of 2-carbethoxy-5-furaldehyde in 20 mL of THF was added over a period of 10 min. The resulting clear yellow solution was stirred at room temperature for 20 h and at 50°-60° C. for 1 h. The mixture was diluted with 500 mL of brine and 300 mL of Et2O. The organic layer was washed twice with 300 mL of brine, dried (Na2SO4), and evaporated to afford 11.0 g of the crude product, which was purified on 150 g of SiO2 (12.5% Et2O/hexane) to give 9.0 g of the pure product as a very pale yellow oil: IR (film) 2990, 2950, 1720, 1670, 1590, 1510, 1460, 1380, 1350, 1320, 1270, 1230, 1190, 1160, 1140, 1030, 980, 850, 800, 760 cm-1 ; 1H NMR (CDCl3) δ1.25 (t, J=7 Hz, 3, CO2CH2CH3), 6.05 (s, 1, C=CH), 6.17 (d, J=4 Hz, 1, 3'H), 7.07 (d, J=4 Hz, 1, 4'H); MS calcd for C11H14O3 194.0943, found 194.0946. maintained at this temperature for 30 min The organic layer was washed twice with 300 mL of brine dried (Na2SO4) evaporated to afford 11.0 g of the crude product, which was purified on 150 g of SiO2 (12.5% Et2O/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Formyl-2-furancarboxylic acid (2.9 g) was dissolved in N,N-dimethylformamide (30 ml), and potassium carbonate (2.9 g) and iodoethane (3.6 g) were added. The mixture was stirred at room temperature for 12 hours, poured into ice water and extracted with diethyl ether. The extract was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and the desired fractions were concentrated under reduced pressure to give 5-formyl- 2-furancarboxylic acid ethyl ester (1.3 g). 5-Formyl-2-furancarboxylic acid ethyl ester (1.3 g) in methylene chloride (5 ml) was slowly added dropwise to diethylaminosulfur trifluoride (DAST) (1.3 g) in methylene chloride (5 ml) at room temperature. The mixture was stirred at room temprature for 30 minutes, and water was added to the mixture. The resulting mixture was extracted with diethyl ether, and the extract was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and the desired fractions were concentrated under reduced pressure to give 5-difluoromethyl-2-furancarboxylic acid ethyl ester (0.7 g). 5-Difluoromethyl-2-furancarboxylic acid ethyl ester (2.3 g) synthesized in this manner was dissolved in ethanol (20 ml), and 1N aqueous sodium hydroxide (15 ml) was added. The mixture was stirred at room temperature and concentrated under reduced paressure. The residue was dissolved in water and washed with diethyl ether. The aqueous layer was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Precipitated crystals were collected by filtration and washed with hexane-isopropyl ether to give 5-difluoromethyl-2-furancarboxylic acid (1.2 g) as crystals. extracted with diethyl ether The extract was washed with water and saturated aqueous sodium chloride dried over anhydrous magnesium sulfate concentrated under reduced pressure the desired fractions were concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Subsequently, ethyl 5-{[(3-phenylpropyl)amino]methyl}-2-furoate (0.64 g) was prepared from ethyl 5-formyl-furan-2-carboxylate (500 mg) and 3-phenylpropylamine (0.85 mL) in the same manner as in Preparation Example 52.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethyl 5-formyl-2-furancarboxylate (5.33 g), 2,3-butanedione-2-oxime (3.21 g) and 4N hydrogenchloride-ethyl acetate solution (100 mL) was stirred at room temperature for 3 days. After concentration of the reaction mixture, diethyl ether was added to the residue and the precipitated crystals were collected by filtration. A mixture of the obtained crystal, tetrahydrofuran (100 mL) and thionyl chloride (5.66 g) was heated under reflux for 3 hrs. The reaction mixture was concentrated and ethyl acetate was added to the residue. The ethyl acetate layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give ethyl 5-(4-chloromethyl-5-methyl-1,3-oxazol-2-yl)-2-furancarboxylate as colorless crystals (2.60 g, yield 30%) from a fraction eluted with ethyl acetate-hexane (1:4, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 117-118° C. the precipitated crystals were collected by filtration A mixture of the obtained crystal, tetrahydrofuran (100 mL) and thionyl chloride (5.66 g) was heated under reflux for 3 hrs The reaction mixture was concentrated ethyl acetate was added to the residue The ethyl acetate layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine dried over anhydrous magnesium sulfate concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethyl 5-formyl-2-furancarboxylate (5.33 g), 2,3-butanedione-2-oxime (3.21 g) and 4N hydrogenchloride-ethyl acetate solution (100 mL) was stirred at room temperature for 3 days. After concentration of the reaction mixture, diethyl ether was added to the residue and the precipitated crystals were collected by filtration. A mixture of the obtained crystal, tetrahydrofuran (100 mL) and thionyl chloride (5.66 g) was heated under reflux for 3 hrs. The reaction mixture was concentrated and ethyl acetate was added to the residue. The ethyl acetate layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give ethyl 5-(4-chloromethyl-5-methyl-1,3-oxazol-2-yl)-2-furancarboxylate as colorless crystals (2.60 g, yield 30%) from a fraction eluted with ethyl acetate-hexane (1:4, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 117-118° C. the precipitated crystals were collected by filtration A mixture of the obtained crystal, tetrahydrofuran (100 mL) and thionyl chloride (5.66 g) was heated under reflux for 3 hrs The reaction mixture was concentrated ethyl acetate was added to the residue The ethyl acetate layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine dried over anhydrous magnesium sulfate concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-benzenesulfonyl-5-methylthioindole (0.5178 g) in tetrahydrofuran (17 ml), n-butyl lithium (1.3 ml, 1.59 M) was added dropwise at −78° C. and the mixture was stirred for 30 minutes, followed by addition of the compound obtained in Example 30 (1) (0.3444 g), and the mixture was stirred at −50° C. for 40 minutes. The reaction solution was poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous NaCl solution, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was separated using silica gel column chromatography (hexane:ethyl acetate=1:1) to obtain 0.593 g of the desired product. the mixture was stirred at −50° C. for 40 minutes extracted with ethyl acetate The organic layer was washed with a saturated aqueous NaCl solution dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The resulting residue was separated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-formyl-2-furancarboxylic acid (0.5 g) in ethanol (35 ml), sulfuric acid (3.5 ml) was added at 0° C. and the mixture was heated under reflux for 5 hours. After cooling, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution and water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was separated using silica gel column chromatography (hexane:ethyl acetate=1:1) to obtain 0.5316 g of the desired product. the mixture was heated under reflux for 5 hours After cooling extracted with ethyl acetate The organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution and water dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The resulting residue was separated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-benzenesulfonyl-5-methylthioindole (0.5178 g) in tetrahydrofuran (17 ml), n-butyl lithium (1.3 ml, 1.59 M) was added dropwise at −78° C. and the mixture was stirred for 30 minutes, followed by addition of the compound obtained in Example 30 (1) (0.3444 g), and the mixture was stirred at −50° C. for 40 minutes. The reaction solution was poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous NaCl solution, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was separated using silica gel column chromatography (hexane:ethyl acetate=1:1) to obtain 0.593 g of the desired product. the mixture was stirred at −50° C. for 40 minutes extracted with ethyl acetate The organic layer was washed with a saturated aqueous NaCl solution dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The resulting residue was separated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-formyl-2-furancarboxylic acid (0.5 g) in ethanol (35 ml), sulfuric acid (3.5 ml) was added at 0° C. and the mixture was heated under reflux for 5 hours. After cooling, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution and water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was separated using silica gel column chromatography (hexane:ethyl acetate=1:1) to obtain 0.5316 g of the desired product. the mixture was heated under reflux for 5 hours After cooling extracted with ethyl acetate The organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution and water dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The resulting residue was separated