diethyl 2-(2-phenylmethoxyethyl)propanedioate

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2.85 g (9.67 mmol equivalents) of diethyl 2-(2-benzyloxyethyl)malonate was dissolved in 20 mL of acetonitrile, 1.60 g (11.7 mmol equivalents) of potassium bicarbonate and 465 mg (11.7 mmol equivalents as formaldehyde) of paraformaldehyde were added thereto, and the mixture was stirred at room temperature (25° C.) overnight. After completion of the reaction, a 0.5 mol/L aqueous solution of hydrochloric acid was added dropwise to the reaction liquid, and the mixture was extracted three times with chloroform. The combined chloroform layers were dried with anhydrous magnesium sulfate and then concentrated under vacuum, and the obtained crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (v/v)=4/1) to give 2.78 g (8.76 mmol equivalents) of diethyl 2-(2-benzyloxyethyl)-2-hydroxymethylmalonate. After completion of the reaction the mixture was extracted three times with chloroform The combined chloroform layers were dried with anhydrous magnesium sulfate concentrated under vacuum the obtained crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (v/v)=4/1)

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

実験手順: 506 mg (60% in oil, 13 mmol equivalents) of sodium hydride was added to 5.0 mL of tetrahydrofuran, and the mixture was cooled to about 0° C. in an ice bath. 3.2 mL (20.7 mmol equivalents) of diethyl malonate was added thereto (solution A). 2.3 g (10.7 mmol equivalents) of 2-benzyloxy-1-bromoethane was dissolved in 3.0 mL of tetrahydrofuran, this was added dropwise to solution A over 10 minutes, and the mixture was refluxed while heating overnight. After completion of the reaction, a 0.5 mol/L aqueous solution of hydrochloric acid was added dropwise to the reaction liquid, and the mixture was extracted three times with diethyl ether. The combined diethyl ether layers were washed with brine, then dried with anhydrous magnesium sulfate, and subsequently concentrated under vacuum, and the obtained crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (v/v)=20/1) to give 2.85 g (9.67 mmol equivalents) of diethyl 2-(2-benzyloxyethyl)malonate. the mixture was refluxed while heating overnight After completion of the reaction the mixture was extracted three times with diethyl ether The combined diethyl ether layers were washed with brine dried with anhydrous magnesium sulfate subsequently concentrated under vacuum the obtained crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (v/v)=20/1)

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

実験手順: 506 mg (60% in oil, 13 mmol equivalents) of sodium hydride was added to 5.0 mL of tetrahydrofuran, and the mixture was cooled to about 0° C. in an ice bath. 3.2 mL (20.7 mmol equivalents) of diethyl malonate was added thereto (solution A). 2.3 g (10.7 mmol equivalents) of 2-benzyloxy-1-bromoethane was dissolved in 3.0 mL of tetrahydrofuran, this was added dropwise to solution A over 10 minutes, and the mixture was refluxed while heating overnight. After completion of the reaction, a 0.5 mol/L aqueous solution of hydrochloric acid was added dropwise to the reaction liquid, and the mixture was extracted three times with diethyl ether. The combined diethyl ether layers were washed with brine, then dried with anhydrous magnesium sulfate, and subsequently concentrated under vacuum, and the obtained crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (v/v)=20/1) to give 2.85 g (9.67 mmol equivalents) of diethyl 2-(2-benzyloxyethyl)malonate. the mixture was refluxed while heating overnight After completion of the reaction the mixture was extracted three times with diethyl ether The combined diethyl ether layers were washed with brine dried with anhydrous magnesium sulfate subsequently concentrated under vacuum the obtained crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (v/v)=20/1)

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

実験手順: The compound was prepared by a modification of the method of Ramalingam et al Tetrahedron, 51, 2875-2894 (1995)]. Thus, sodium (1.20 g) was dissolved in absolute ethanol (25 mL) under argon. Diethyl malonate (14.00 g) was added and the mixture was refluxed for 30 min. Benzyl bromoethyl ether (10 g) was added and the mixture was stirred at reflux for 16 hours. The ethanol was removed by rotary evaporation and the residue was partitioned between ether (100 mL) and water (50 mL). The ethereal layer was washed with water (3×50 mL) and dried over sodium sulfate. The ether was removed by rotary evaporation and the residue was distilled in vacuoo. The fraction distilling at 40-55° C. was discarded (unreacted diethyl malonate). The product distilled at 140-150° C. (1 mm), [lit. bp 138-140 C (1 mm)]. The yield was 12.60 g of colourless oil. The compound was prepared by a modification of the method of Ramalingam et al Tetrahedron, 51, 2875-2894 (1995)] the mixture was refluxed for 30 min at reflux for 16 hours The ethanol was removed by rotary evaporation the residue was partitioned between ether (100 mL) and water (50 mL) The ethereal layer was washed with water (3×50 mL) dried over sodium sulfate The ether was removed by rotary evaporation the residue was distilled in vacuoo The fraction distilling at 40-55° C. The product distilled at 140-150° C. (1 mm), [lit. bp 138-140 C (1 mm)]

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

実験手順: To a cooled, stirred suspension of lithium aluminum hydride (103 g, 2.7 mol) in dry ether (2.51) under nitrogen was added ethyl 4-benzyloxy-2-ethoxycarbonyl-butanoate (362 g, 1.23 mol) over a period of 3 hours. On completion of the addition, the reaction mixture was allowed to warm to room temperature, and then heated under reflux for 1 hour. It was then re-cooled and the excess lithium aluminium hydride destroyed by dropwise addition of water (100 ml), 2 M sodium hydroxide (100 ml) and water (300 ml). The reaction mixture was filtered, and the filter cake washed well with chloroform. The filtrate was dried (MgSO4), filtered, and evaporated to give 4-benzyloxy-2-hydroxymethylbutan-1-ol as a clear oil (226 g, 87%). δH (CDCl3) 1.35-2.05 (3 H, m, CHCH2CH2), 3.30-3.80 (8 H, m, 3×CH2O, 2×OH), 4.42 (2 H, s, OCH2Ph), 7.26 (5 H, s, Ar). On completion of the addition heated under reflux for 1 hour It was then re-cooled the excess lithium aluminium hydride destroyed by dropwise addition of water (100 ml), 2 M sodium hydroxide (100 ml) and water (300 ml) The reaction mixture was filtered the filter cake washed well with chloroform The filtrate was dried (MgSO4) filtered evaporated

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

実験手順: To a cooled, stirred suspension of lithium aluminium hydride (103 g, 2.7 mol) in dry ether (2.51) under nitrogen was added ethyl 4-benzyloxy-2-ethoxycarbonyl-butanoate (362 g, 1.23 mol) over a period of 3 hours. On completion of the addition, the reaction mixture was allowed to warm to room temperature, and then heated under reflux for 1 hour. It was then re-cooled and the excess lithium aluminium hydride destroyed by dropwise addition of water (100 ml), 2M sodium hydroxide (100 ml) and water (300 ml). The reaction mixture was filtered, and the filter cake washed well with chloroform. The filtrate was dried (MgSO4), filtered, and evaporated to give 4-benzyloxy-2-hydroxymethylbutan-1-ol as a clear oil (226 g, 87%). δH (CDCl3) 1.35-2.05 (3H, m, CHCH2CH2), 3.30-3.80 (8H, m, 3×CH2O, 2×OH), 4.42 (2H, s, OCH2Ph) 7.26 (5H, s, Ar). On completion of the addition heated under reflux for 1 hour It was then re-cooled the excess lithium aluminium hydride destroyed by dropwise addition of water (100 ml), 2M sodium hydroxide (100 ml) and water (300 ml) The reaction mixture was filtered the filter cake washed well with chloroform The filtrate was dried (MgSO4) filtered evaporated

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

実験手順: To a cooled, stirred suspension of lithium aluminium hydride (103 g, 2.7 mol) in dry ether (2.51) under nitrogen was added ethyl 4-benzyloxy-2-ethoxycarbonyl-butanoate (362 g, 1.23 mol) over a period of 3 hours. On completion of the addition, the reaction mixture was allowed to warm to room temperature, and then heated under reflux for 1 hour. It was then re-cooled and the excess lithium aluminium hydride destroyed by dropwise addition of water (100 ml), 2M sodium hydroxide (100 ml) and water (300 ml). The reaction mixture was filtered, and the filter cake washed well with chloroform. The filtrate was dried (MgSO4), filtered, and evaporated to give 4-benzyloxy-2-hydroxymethylbutan-1-ol as a clear oil (226 g, 87%). δH (CDCl3) 1.35-2.05 (3H, m, CHCH2CH2), 3.30-3.80 (8H, m, 3×CH2O, 2×OH), 4.42 (2H, s, OCH2Ph), 7.26 (5H, s, Ar). On completion of the addition heated under reflux for 1 hour It was then re-cooled the excess lithium aluminium hydride destroyed by dropwise addition of water (100 ml), 2M sodium hydroxide (100 ml) and water (300 ml) The reaction mixture was filtered the filter cake washed well with chloroform The filtrate was dried (MgSO4) filtered evaporated

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2.85 g (9.67 mmol equivalents) of diethyl 2-(2-benzyloxyethyl)malonate was dissolved in 20 mL of acetonitrile, 1.60 g (11.7 mmol equivalents) of potassium bicarbonate and 465 mg (11.7 mmol equivalents as formaldehyde) of paraformaldehyde were added thereto, and the mixture was stirred at room temperature (25° C.) overnight. After completion of the reaction, a 0.5 mol/L aqueous solution of hydrochloric acid was added dropwise to the reaction liquid, and the mixture was extracted three times with chloroform. The combined chloroform layers were dried with anhydrous magnesium sulfate and then concentrated under vacuum, and the obtained crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (v/v)=4/1) to give 2.78 g (8.76 mmol equivalents) of diethyl 2-(2-benzyloxyethyl)-2-hydroxymethylmalonate. After completion of the reaction the mixture was extracted three times with chloroform The combined chloroform layers were dried with anhydrous magnesium sulfate concentrated under vacuum the obtained crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (v/v)=4/1)

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

実験手順: 506 mg (60% in oil, 13 mmol equivalents) of sodium hydride was added to 5.0 mL of tetrahydrofuran, and the mixture was cooled to about 0° C. in an ice bath. 3.2 mL (20.7 mmol equivalents) of diethyl malonate was added thereto (solution A). 2.3 g (10.7 mmol equivalents) of 2-benzyloxy-1-bromoethane was dissolved in 3.0 mL of tetrahydrofuran, this was added dropwise to solution A over 10 minutes, and the mixture was refluxed while heating overnight. After completion of the reaction, a 0.5 mol/L aqueous solution of hydrochloric acid was added dropwise to the reaction liquid, and the mixture was extracted three times with diethyl ether. The combined diethyl ether layers were washed with brine, then dried with anhydrous magnesium sulfate, and subsequently concentrated under vacuum, and the obtained crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (v/v)=20/1) to give 2.85 g (9.67 mmol equivalents) of diethyl 2-(2-benzyloxyethyl)malonate. the mixture was refluxed while heating overnight After completion of the reaction the mixture was extracted three times with diethyl ether The combined diethyl ether layers were washed with brine dried with anhydrous magnesium sulfate subsequently concentrated under vacuum the obtained crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (v/v)=20/1)

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

実験手順: The compound was prepared by a modification of the method of Ramalingam et al Tetrahedron, 51, 2875-2894 (1995)]. Thus, sodium (1.20 g) was dissolved in absolute ethanol (25 mL) under argon. Diethyl malonate (14.00 g) was added and the mixture was refluxed for 30 min. Benzyl bromoethyl ether (10 g) was added and the mixture was stirred at reflux for 16 hours. The ethanol was removed by rotary evaporation and the residue was partitioned between ether (100 mL) and water (50 mL). The ethereal layer was washed with water (3×50 mL) and dried over sodium sulfate. The ether was removed by rotary evaporation and the residue was distilled in vacuoo. The fraction distilling at 40-55° C. was discarded (unreacted diethyl malonate). The product distilled at 140-150° C. (1 mm), [lit. bp 138-140 C (1 mm)]. The yield was 12.60 g of colourless oil. The compound was prepared by a modification of the method of Ramalingam et al Tetrahedron, 51, 2875-2894 (1995)] the mixture was refluxed for 30 min at reflux for 16 hours The ethanol was removed by rotary evaporation the residue was partitioned between ether (100 mL) and water (50 mL) The ethereal layer was washed with water (3×50 mL) dried over sodium sulfate The ether was removed by rotary evaporation the residue was distilled in vacuoo The fraction distilling at 40-55° C. The product distilled at 140-150° C. (1 mm), [lit. bp 138-140 C (1 mm)]