ethyl 3-oxo-4-phenylmethoxybutanoate

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: 300.0 g (1.27 moles) ethyl 4-benzyloxy-3-oxobutyrate, 300 ml ethanol, and 104.5 mg (0.127 mmol) [RuCl{(S)-segphos}]2(μ-Cl)3[Me2NH2] were introduced in a nitrogen stream into a 1-L autoclave and flushed with hydrogen, and after introduction of hydrogen at a pressure of 1 MPa, the mixture was heated with stirring. The mixture was reacted at 90 to 95° C. for 7 hours. After the reaction solution was cooled to room temperature, the hydrogen was purged and replaced by nitrogen. The reaction solution was concentrated in a rotary evaporator and the residue was distilled under reduced pressure to give 265.1 g of the title compound (chemical purity, 95.5%; optical purity, 99.1% ee; and yield, 87.6%). flushed with hydrogen after introduction of hydrogen at a pressure of 1 MPa, the mixture was heated The mixture was reacted at 90 to 95° C. for 7 hours the hydrogen was purged The reaction solution was concentrated in a rotary evaporator the residue was distilled under reduced pressure

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

実験手順: 300.0 g (1.27 moles) ethyl 4-benzyloxy-3-oxobutyrate, 300 ml ethanol, and 104.5 mg (0.127 mmol) [RuCl{(R)-segphos}]2(μ-Cl)3 [Me2NH2] were introduced in a nitrogen stream into a 1-L autoclave and flushed with hydrogen, and after introduction of hydrogen at a pressure of 1 MPa, the mixture was heated with stirring. The mixture was reacted at 90 to 95° C. for 7 hours. After the reaction solution was cooled to room temperature, the hydrogen was purged and replaced by nitrogen. The reaction solution was concentrated in a rotary evaporator and the residue was distilled under reduced pressure to give 263.3 g of the title compound (chemical purity, 96.2%; optical purity, 99.1% ee; and yield, 87%). flushed with hydrogen after introduction of hydrogen at a pressure of 1 MPa, the mixture was heated The mixture was reacted at 90 to 95° C. for 7 hours the hydrogen was purged The reaction solution was concentrated in a rotary evaporator the residue was distilled under reduced pressure

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

実験手順: To a stirred suspension of NaH (3 g, 0.1 mmol, 80% oil dispersion previously washed with hexanes), in THF (75 ml, distilled from Na) was added dropwise neat benzyl alcohol (10.3 g, 0.1 mmol) at rt. Stirring was continued until H2 evolution had ceased, then ethyl 4-chloroacetoacetate (8.23 g, 0.05 mmol) in THF (20 ml) was added dropwise to this solution in a cooling water bath. The reaction was stirred at rt overnight. The mixture was partitioned between ether and 1N HCl, the layers separated, and the aqueous further extracted with ether (x 2). The combined ether extracts were washed twice with water and then brine and dried (Na2SO4), filtered, and concentrated in vacuo to give 17.83 g crude product. Distillation (119-124° C., 0.2 mm Hg) afforded a yellow oil. (7.34 g, 62%) previously washed with hexanes), in THF (75 ml, distilled from Na) The reaction was stirred at rt overnight The mixture was partitioned between ether and 1N HCl the layers separated the aqueous further extracted with ether (x 2) The combined ether extracts were washed twice with water brine and dried (Na2SO4) filtered concentrated in vacuo

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 80 g of 60% NaH are added in portions to 800 ml of anhydrous THF. The medium is cooled to 10° C. and maintained at this temperature. 500 ml of benzyl alcohol are then introduced dropwise. A solution of 65.8 g of ethyl 4-chloroacetoacetate in 200 ml of benzyl alcohol is then added. The mixture is stirred at room temperature for 20 h. It is neutralized by the slow addition of acetic acid (120 ml) while being cooled with an ice bath. The whole is then poured into a mixture of water and ice and extracted with ether. The organic phase is washed with a solution of sodium bicarbonate, dried over MgSO4 and then concentrated to give an orange oil. The product is purified by two successive distillations to give a yellow oil. maintained at this temperature while being cooled with an ice bath extracted with ether The organic phase is washed with a solution of sodium bicarbonate dried over MgSO4 concentrated to give an orange oil The product is purified by two successive distillations to give a yellow oil

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 80 g of 60% NaH are added in portions to 800 ml of anhydrous THF. The medium is cooled to 10° C. and maintained at this temperature. 500 ml of benzyl alcohol are then introduced dropwise. A solution of 65.8 g of ethyl 4-chloroacetoacetate in 200 ml of benzyl alcohol is then added. The mixture is stirred at room temperature for 20 h. It is neutralized by the slow addition of acetic acid (120 ml) while being cooled with an ice bath. The whole is then poured into a mixture of water and ice and extracted with ether. The organic phase is washed with a solution of sodium bicarbonate, dried over MgSO4 and then concentrated to give an orange oil. The product is purified by two successive distillations to give a yellow oil. maintained at this temperature while being cooled with an ice bath extracted with ether The organic phase is washed with a solution of sodium bicarbonate dried over MgSO4 concentrated to give an orange oil The product is purified by two successive distillations to give a yellow oil

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 80 g of 60% NaH are added in portions to 800 ml of anhydrous THF. The medium is cooled to 10° C. and maintained at this temperature. 500 ml of benzyl alcohol are then introduced dropwise. A solution of 65.8 g of ethyl 4-chloroacetoacetate in 200 ml of benzyl alcohol is then added. The mixture is stirred at room temperature for 20 h. It is neutralized by the slow addition of acetic acid (120 ml) while being cooled with an ice bath. The whole is then poured into a mixture of water and ice and extracted with ether. The organic phase is washed with a solution of sodium bicarbonate, dried over MgSO4 and then concentrated to give an orange oil. The product is purified by two successive distillations to give a yellow oil. maintained at this temperature while being cooled with an ice bath extracted with ether The organic phase is washed with a solution of sodium bicarbonate dried over MgSO4 concentrated to give an orange oil The product is purified by two successive distillations to give a yellow oil

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 80 g of 60% NaH are added in portions to 800 ml of anhydrous THF. The medium is cooled to 10° C. and maintained at this temperature. 500 ml of benzyl alcohol are then introduced dropwise. A solution of 65.8 g of ethyl 4-chloroacetoacetate in 200 ml of benzyl alcohol is then added. The mixture is stirred at room temperature for 20 h. It is neutralized by the slow addition of acetic acid (120 ml) while being cooled with an ice bath. The whole is then poured into a mixture of water and ice and extracted with ether. The organic phase is washed with a solution of sodium bicarbonate, dried over MgSO4 and then concentrated to give an orange oil. The product is purified by two successive distillations to give a yellow oil. maintained at this temperature while being cooled with an ice bath extracted with ether The organic phase is washed with a solution of sodium bicarbonate dried over MgSO4 concentrated to give an orange oil The product is purified by two successive distillations to give a yellow oil

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

実験手順: Ethyl 4-benzyloxyacetoacetate (42.1 g) synthesized according to the method describe in U.S. Pat. No. 5,399,722 was dissolved in methanol (300 mL) and sodium borohydride (3.03 g) was added at a temperature of from 5° C. to 10° C. The mixture was stirred for 1 hr and water (300 mL) was added. The solvent was mostly evaporated, and the organic layer extracted twice with MTBE (30b mL) was washed twice with 2% sodium hydrogen carbonate (100 mL) and washed twice with saturated brine (150 mL), dried over anhydrous magnesium sulfate and filtrated. MTBE was evaporated to give ethyl (±)-4-benzyloxy-3-hydroxybutanoate (38.8 g). To a solution of lithium diisopropylamide 1.5 M cyclohexane solution (190 mL) in THF (200 mL) was added a solution of ethyl (±)-4-benzyloxy-3-hydroxybutanoate (29.4 g) in THF (50 mL) at a temperature of from −78° C. to −60° C. and the temperature was raised to −20° C. Separately, 2-iodoethanol (34.4 g) and ethyl vinyl ether (23.1 g) were mixed in the presence of p-toluenesulfonic acid monohydrate (20 mg) to give 2-(1-ethoxyethoxy)ethyl iodide (47.9 g) and 39.3 g thereof was added dropwise at a temperature near −20° C. to 0° C. The mixture was stirred overnight at room temperature. The reaction mixture was poured into a 1N aqueous hydrochloric acid (450 mL), and the mixture was extracted twice with MTBE (200 mL) and washed with saturated aqueous sodium hydrogen carbonate solution. The solvent was evaporated and methanol (300 mL) and p-toluenesulfonic acid monohydrate (5.3 g) were added to the residue. The mixture was stirred at room temperature for 6 hr. Triethylamine (2.0 g) was added to the reaction mixture and the solvent was mostly evaporated. The residue was extracted with ethyl acetate (300 mL). The organic layer was washed with water (150 mL) and saturated aqueous sodium hydrogen carbonate solution (150 mL) and dried over anhydrous magnesium sulfate. The solvent was evaporated. Diisopropyl ether (120 mL) was added to the residue and the mixture was recrystallized to give the title compound (5.65 g) (yellow fine crystals). The peak of syn-form (1′R*,2R*-body) was not detected in NMR and HPLC under the following conditions. The solvent was mostly evaporated the organic layer extracted twice with MTBE (30b mL) was washed twice with 2% sodium hydrogen carbonate (100 mL) washed twice with saturated brine (150 mL) dried over anhydrous magnesium sulfate filtrated MTBE was evaporated

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

実験手順: 21.24 g of the 4-benzyloxyacetoacetic ethyl ester dissolved in acetic ester (100 ml) was inserted into a 200 ml steel autoclave provided with a magnetic stirrer and was hydrogenolized in the presence of 1.05 g Pd 5 percent on coal with hydrogen with a pressure of 5 atm. After the reaction was completed, which amounted to a period of about 2 hours, and after a 2 hour post-reaction time, the catalyst was filtered out. The filtrate was evaporated on a vacuum rotation evaporator at 35° C. The residue was dried in the high vacuum. 13.4 g of 4-hydroxyacetoacetic ethyl ester in the form of a slightly yellowish oil resulted. provided with a magnetic stirrer after a 2 hour post-reaction time the catalyst was filtered out The filtrate was evaporated on a vacuum rotation evaporator at 35° C The residue was dried in the high vacuum

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

実験手順: 21.24 g of the 4-benzyloxyacetoacetic ethyl ester dissolved in acetic ester (100 ml) was inserted into a 200 ml steel autoclave provided with a magnetic stirrer and was hydrogenolized in the presence of 1.05 g Pd 5 percent on coal with hydrogen with a pressure of 5 atm. After the reaction was completed, which amounted to a period of about 2 hours, and after a 2 hour post-reaction time, the catalyst was filtered out. The filtrate was evaporated on a vacuum rotation evaporator at 35° C. The residue was dried in the high vacuum. 13.4 g of 4-hydroxyacetoacetic ethyl ester in the form of a slightly yellowish oil resulted. provided with a magnetic stirrer after a 2 hour post-reaction time the catalyst was filtered out The filtrate was evaporated on a vacuum rotation evaporator at 35° C The residue was dried in the high vacuum

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

実験手順: 300.0 g (1.27 moles) ethyl 4-benzyloxy-3-oxobutyrate, 300 ml ethanol, and 104.5 mg (0.127 mmol) [RuCl{(S)-segphos}]2(μ-Cl)3[Me2NH2] were introduced in a nitrogen stream into a 1-L autoclave and flushed with hydrogen, and after introduction of hydrogen at a pressure of 1 MPa, the mixture was heated with stirring. The mixture was reacted at 90 to 95° C. for 7 hours. After the reaction solution was cooled to room temperature, the hydrogen was purged and replaced by nitrogen. The reaction solution was concentrated in a rotary evaporator and the residue was distilled under reduced pressure to give 265.1 g of the title compound (chemical purity, 95.5%; optical purity, 99.1% ee; and yield, 87.6%). flushed with hydrogen after introduction of hydrogen at a pressure of 1 MPa, the mixture was heated The mixture was reacted at 90 to 95° C. for 7 hours the hydrogen was purged The reaction solution was concentrated in a rotary evaporator the residue was distilled under reduced pressure