ethyl 2-(2-formylphenoxy)acetate

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

実験手順: To a suspension of 260 mg of [4-(4-phenylbutoxy)-2methoxybenzyl]triphenylphosphonium choride obtained in Reference Example 22 in 2.5 ml of tetrahydrofuran was dropwise added 0.36 ml of a 1.42M n-butyl lithium/hexane solution. The mixture was stirred for 10 minutes to form a dark red solution The solution was dropwise added to a solution of 114 mg of ethyl o-formylphenoxyacetate in 1 ml of tetrahydrofuran at 0° C. using an injection tube. After stirring for 20 minutes, a saturated ammonium chloride aqueous solution was added thereto. The product was extracted with ether. After washing with water and then an aqueous saline solution, the ethereal layer was dried and concentrated. The crude product was fractionated and separated by TLC (developer; hexane : methylene chloride acetone=8:2:1) to obtain 170 mg of ethyl o-[3-methoxy-4-(4-phenylbutoxy)styryl]phenoxyacetate. to form a dark red solution The solution After stirring for 20 minutes The product was extracted with ether After washing with water an aqueous saline solution, the ethereal layer was dried concentrated separated by TLC (developer; hexane : methylene chloride acetone=8:2:1)

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

実験手順: To a suspension of 260 mg of [4-(4-phenylbutoxy)-2-methoxybenzyl]triphenylphosphonium choride obtained in Reference Example 22 in 2.5 ml of tetrahydrofuran was dropwise added 0.36 ml of a 1.42M n-butyl lithium/hexane solution. The mixture was stirred for 10 minutes to form a dark red solution. The solution was dropwise added to a solution of 114 mg of ethyl o-formylphenoxyacetate in 1 ml of tetrahydrofuran at 0° C. using an injection tube. After stirring for 20 minutes, a saturated ammonium chloride aqueous solution was added thereto. The product was extracted with ether. After washing with water and then an aqueous saline solution, the ethereal layer was dried and concentrated. The crude product was fractionated and separated by TLC (developer; hexane:methylene chloride:acetone=8:2:1) to obtain 170 mg of ethyl o-[3-methoxy-4-(4-phenylbutoxy)styryl]phenoxyacetate. to form a dark red solution After stirring for 20 minutes The product was extracted with ether After washing with water an aqueous saline solution, the ethereal layer was dried concentrated separated by TLC (developer; hexane:methylene chloride:acetone=8:2:1)

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

実験手順: To a suspension of 260 mg of [4-(4-phenylbutoxy)-2-methoxybenzyl]triphenylphosphonium choride obtained in Reference Example 22 in 2.5 ml of tetrahydrofuran was dropwise added 0.36 ml of a 1.42M n-butyl lithium/hexane solution. The mixture was stirred for 10 minutes to form a dark red solution. The solution was dropwise added to a solution of 114 mg of ethyl o-formylphenoxyacetate in 1 ml of tetrahydrofuran at 0° C. using an injection tube. After stirring for 20 minutes, a saturated ammonium chloride aqueous solution was added thereto. The product was extracted with ether. After washing with water and then an aqueous saline solution, the ethereal layer was dried and concentrated. The crude product was fractionated and separated by TLC (developer; hexane:methylene chloride:acetone=8:2:1) to obtain 170 mg of ethyl o-[3-methoxy-4-(4-phenylbutoxy)styryl]phenoxyacetate. to form a dark red solution After stirring for 20 minutes The product was extracted with ether After washing with water an aqueous saline solution, the ethereal layer was dried concentrated separated by TLC (developer; hexane:methylene chloride:acetone=8:2:1)

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

実験手順: A mixture of 1-cyclopentyl-3-ethyl-5-amino-1H-pyrazole-4-carboxamide (5.26 g, 23.7 mmol), 2-(ethoxycarbonylmethoxy)benzaldehyde (9.10 g, 47.3 mmol), p-toluenesulfonic acid (0.2 g) and xylenes (100 ml) was refluxed for 18 hours with the azeotropic removal of water. The solvent was removed in vacuo, and the residue was treated with ethanol and evaporated to dryness. The residue was partitioned between chloroform and 10% aqueous K2CO3, the layers were separated and the aqueous layer was extracted with chloroform (100 ml). The organic layers were combined, and concentrated to dryness. The residue was preloaded on silica gel and then was purified by column chromatography on silica gel eluting with hexanes (100%) to 20% ether/hexane to afford 3.74 g (38%) of 1-cyclopentyl-3-ethyl-6-[2-(ethoxycarbonylmethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-one, m.p. 116-117° C. The solvent was removed in vacuo the residue was treated with ethanol evaporated to dryness The residue was partitioned between chloroform and 10% aqueous K2CO3 the layers were separated the aqueous layer was extracted with chloroform (100 ml) concentrated to dryness was purified by column chromatography on silica gel eluting with hexanes (100%) to 20% ether/hexane

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

実験手順: A mixture of 1-cyclopentyl-3-ethyl-5-amino-1H-pyrazole-4-carboxamide (5.26 g, 23.7 mmol), 2-(ethoxycarbonylmethoxy)benzaldehyde (9.10 g, 47.3 mmol), p-toluenesulfonic acid (0.2 g) and xylenes (100 ml) was refluxed for 18 hours with the azeotropic removal of water. The solvent was removed in vacuo, and the residue was treated with ethanol and evaporated to dryness. The residue was partitioned between chloroform and 10% aqueous K2CO3, the layers were separated and the aqueous layer was extracted with chloroform (100 ml). The organic layers were combined, and concentrated to dryness. The residue was preloaded on silica gel and then was purified by column chromatography on silica gel eluting with hexanes (100%) to 20% ether/hexane to afford 3.74 g (38%) of 1-cyclopentyl-3-ethyl-6-[2-(ethoxycarbonylmethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-4-one, m.p. 116-117° C. The solvent was removed in vacuo the residue was treated with ethanol evaporated to dryness The residue was partitioned between chloroform and 10% aqueous K2CO3 the layers were separated the aqueous layer was extracted with chloroform (100 ml) concentrated to dryness was purified by column chromatography on silica gel eluting with hexanes (100%) to 20% ether/hexane

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

実験手順: A mixture of 2-formylphenoxyacetic acid (9.01 g, 0.05 mol), ethanol (4.6 g), concentrated H2SO4 (0.4 ml) and toluene (40 ml) was heated to reflux with azeotropic removal of water for 1 hour. The reaction mixture was poured into 10% KHCO3 (100 ml), the layers were separated and the aqueous layer was extracted with ether (2×75 ml). The organic layers were combined, and concentrated in vacuo to afford 9.1 g (95%) of 2-(ethoxycarbonylmethoxy)benzaldehyde. was heated the layers were separated the aqueous layer was extracted with ether (2×75 ml) concentrated in vacuo

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

実験手順: A solution of 21.2 g of morpholine enamine of cyclopentanone, 24.0 g of 2-formylphenoxyacetic acid ethyl ester, and 200 ml of benzene was refluxed through a condenser equipped with a Dean-Stark trap for about 4.5 hours. The resulting solution was cooled to about room temperature, and treated with 35 ml of 6 normal (N) hydrochloric acid. After stirring for about 2 hours at about room temperature, the benzene layer was separated and the aqueous layer was extracted with two 15 ml portions of benzene. The combined benzene layer and extracts were washed with 5% sodium bicarbonate and saturated sodium chloride solution and dried over anhydrous magnesium sulfate. After removal of the solvent in vacuo, 27.6 g of nearly pure product was obtained. The product was crystallized in 50% ethanol to give 26.0 g of 2-(E)-(2-ethoxycarbonylmethoxyl-benzylidene) cyclopentanone as colorless crystals. The melting point of this intermediate compound was determined to be 77°-79° C. equipped with a Dean-Stark trap for about 4.5 hours The resulting solution was cooled to about room temperature the benzene layer was separated the aqueous layer was extracted with two 15 ml portions of benzene The combined benzene layer and extracts were washed with 5% sodium bicarbonate and saturated sodium chloride solution dried over anhydrous magnesium sulfate After removal of the solvent in vacuo, 27.6 g of nearly pure product was obtained The product was crystallized in 50% ethanol

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

実験手順: A mixture of 1-cyclopentyl-3-ethyl-5-amino-1H-pyrazole-4-carboxamide (5.26 g, 23.7 mmol), 2-(ethoxycarbonylmethoxy) benzaldehyde (9.10 g, 47.3 mmol), p-toluenesulfonic acid (0.2 g) and xylenes (100 ml) was refluxed for 18 hours with the azeotropic removal of water. The solvent was removed in vacuo, and the residue was treated with ethanol and evaporated to dryness. The residue was partitioned between chloroform and 10% aqueous K2 CO3, the layers were separated and the aqueous layer was extracted with chloroform (100 ml). The organic layers were combined, and concentrated to dryness. The residue was preloaded on silica gel and then was purified by column chromatography on silica gel eluting with hexanes (100%) to 20% ether/hexane to afford 3.74 g (38%) of 1-cyclopentyl-3-ethyl-6-[2-(ethoxycarbonylmethoxy)phenyl]pyrazolo [3,4-d]pyrimidin-4-one, m.p. 116°-117° C. The solvent was removed in vacuo the residue was treated with ethanol evaporated to dryness The residue was partitioned between chloroform and 10% aqueous K2 CO3 the layers were separated the aqueous layer was extracted with chloroform (100 ml) concentrated to dryness was purified by column chromatography on silica gel eluting with hexanes (100%) to 20% ether/hexane

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

実験手順: A mixture of 2-formylphenoxyacetic acid (9.01 g, 0.05 mol), ethanol (4.6 g), concentrated H2SO4 (0.4 ml) and toluene (40 ml) was heated to reflux with azeotropic removal of water for 1 hour. The reaction mixture was poured into 10% KHCO3 (100 ml), the layers were separated and the aqueous layer was extracted with ether (2×75 ml). The organic layers were combined, and concentrated in vacuo to afford 9.1 g (95%) of 2-(ethoxycarbonylmethoxy)benzaldehyde. was heated the layers were separated the aqueous layer was extracted with ether (2×75 ml) concentrated in vacuo

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

実験手順: To a suspension of 260 mg of [4-(4-phenylbutoxy)-2-methoxybenzyl]triphenylphosphonium chloride obtained in Reference Example 22 in 2.5 ml of tetrahydrofuran was dropwise added 0.36 ml of a 1.42M n-butyl lithium/hexane solution. The mixture was stirred for 10 minutes to form a dark red solution The solution was dropwise added to a solution of 114 mg of ethyl o-formylphenoxyacetate in 1 ml of tetrahydrofuran at 0° C. using an injection tube. After stirring for °minutes, a saturated ammonium chloride aqueous solution was added thereto. The product was extracted with ether. After washing with water and then an aqueous saline solution, the ethereal layer was dried and concentrated. The crude product was fractionated and separated by TLC (developer; hexane:methylene chloride:acetone =8:2:1) to obtain 170 mg of ethyl o-[3-methoxy-4-(4-phenylbutoxy)styryl]phenoxyacetate. to form a dark red solution The solution After stirring for °minutes The product was extracted with ether After washing with water an aqueous saline solution, the ethereal layer was dried concentrated separated by TLC (developer; hexane:methylene chloride:acetone =8:2:1)

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

実験手順: To a suspension of 260 mg of [4-(4-phenylbutoxy)-2methoxybenzyl]triphenylphosphonium choride obtained in Reference Example 22 in 2.5 ml of tetrahydrofuran was dropwise added 0.36 ml of a 1.42M n-butyl lithium/hexane solution. The mixture was stirred for 10 minutes to form a dark red solution The solution was dropwise added to a solution of 114 mg of ethyl o-formylphenoxyacetate in 1 ml of tetrahydrofuran at 0° C. using an injection tube. After stirring for 20 minutes, a saturated ammonium chloride aqueous solution was added thereto. The product was extracted with ether. After washing with water and then an aqueous saline solution, the ethereal layer was dried and concentrated. The crude product was fractionated and separated by TLC (developer; hexane : methylene chloride acetone=8:2:1) to obtain 170 mg of ethyl o-[3-methoxy-4-(4-phenylbutoxy)styryl]phenoxyacetate. to form a dark red solution The solution After stirring for 20 minutes The product was extracted with ether After washing with water an aqueous saline solution, the ethereal layer was dried concentrated separated by TLC (developer; hexane : methylene chloride acetone=8:2:1)

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

実験手順: To a suspension of 260 mg of [4-(4-phenylbutoxy)-2-methoxybenzyl]triphenylphosphonium choride obtained in Reference Example 22 in 2.5 ml of tetrahydrofuran was dropwise added 0.36 ml of a 1.42M n-butyl lithium/hexane solution. The mixture was stirred for 10 minutes to form a dark red solution. The solution was dropwise added to a solution of 114 mg of ethyl o-formylphenoxyacetate in 1 ml of tetrahydrofuran at 0° C. using an injection tube. After stirring for 20 minutes, a saturated ammonium chloride aqueous solution was added thereto. The product was extracted with ether. After washing with water and then an aqueous saline solution, the ethereal layer was dried and concentrated. The crude product was fractionated and separated by TLC (developer; hexane:methylene chloride:acetone=8:2:1) to obtain 170 mg of ethyl o-[3-methoxy-4-(4-phenylbutoxy)styryl]phenoxyacetate. to form a dark red solution After stirring for 20 minutes The product was extracted with ether After washing with water an aqueous saline solution, the ethereal layer was dried concentrated separated by TLC (developer; hexane:methylene chloride:acetone=8:2:1)