methyl 3-cyclopentylpropanoate

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

実験手順: To a solution of dimethyl methylphosphonate (2.17 ml, 20 mmol) in anhydrous THF (20 mL), cooled at −78° C. was added n-BuLi (1.6 M in hexane, 13.7 mL, 22 mmol). The mixture was stirred for 30 minutes at this temperature under nitrogen. Methyl 3-cyclopentylpropanoate (1.56 g, 10 mmol), prepared from 3-cyclopentylpropionic acid (Aldrich) and methanol at the presence of the catalytic amount of the concentrated sulfuric acid (the procedure described in Intermediate 17.1), was added dropwise for 10 minutes. The mixture was stirred for 2 hours at −78° C., gradually was warm to room temperature. The mixture was quenched with addition of 1N HCl to pH 4-5. The organic layer was separated, washed with brine and dried over MgSO4. The residue was purified through flash chromatography on silica gel (EtOAc:Hexanes=1:1) to give the product (1.80 g) with colorless oil in 82% yield. 1HNMR (CD3OD, ppm) δ 1.03 (m, 2H), 1.51 (m, 1H), 1.61 (m, 6H), 1.73 (m, 2H), 2.63 (t, J=7.4 Hz, 2H), 3.09 (d, J=22.7 Hz, 2H), 3.76 (s, 3H), 3.87 (s, 3H) was added dropwise for 10 minutes The mixture was stirred for 2 hours at −78° C. The mixture was quenched with addition of 1N HCl to pH 4-5 The organic layer was separated washed with brine dried over MgSO4 The residue was purified through flash chromatography on silica gel (EtOAc:Hexanes=1:1)

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

実験手順: 203 ml 1.6M Butyllithium in hexane were added to a solution of 46.0 ml diisopropylamine in 120 ml THF at 0° over 1 h. The resultant LDA-solution was stirred at 0° for 1 h and then cooled down to −75°. 50.8 g 3-cyclopentyl-propionic acid methylester dissolved in 65 ml THF were added at −75° over 1 h and stirring at that temperature was continued for 1 h. 67.6 g 3-(3-tert-butoxy-2-oxo-propyl)-1,5,5-trimethyl-imidazolidine-2,4-dione dissolved in 65 ml THF were added at −75° over 1 h and after additional stirring at −75° for 1 h, 50 ml conc. H2SO4 were added over 15 minutes. The reaction mixture was refluxed for 3 h, cooled down to r.t. and hydrolyzed with 300 ml deionized water. The organic layer was separated, washed with 10% brine and dried over Na2SO4. Filtration and evaporation of the solvent afforded 96.5 g crude 3-(4-cyclopentylmethyl-3-hydroxy-5-oxo-tetrahydro-furan-3-ylmethyl)-(1,5,5-trimethyl-imidazolidine-2,4-dione as a yellow oil, which was used without purification for the next step. 3-Cyclopentyl-propionic acid methylester was prepared from the corresponding acid (ACROS No. 11161). The methylester is also available at Chemische Fabrik K. Bucher. cooled down to −75° were added at −75° over 1 h were added at −75° over 1 h after additional stirring at −75° for 1 h The reaction mixture was refluxed for 3 h The organic layer was separated washed with 10% brine dried over Na2SO4 Filtration and evaporation of the solvent

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

実験手順: 203 ml 1.6M Butyllithium in hexane were added to a solution of 46.0 ml diisopropylamine in 120 ml THF at 0° over 1 h. The resultant LDA-solution was stirred at 0° for 1 h and then cooled down to −75°. 50.8 g 3-cyclopentyl-propionic acid methylester dissolved in 65 ml THF were added at −75° over 1 h and stirring at that temperature was continued for 1 h. 67.6 g 3-(3-tert-butoxy-2-oxo-propyl)-1,5,5-trimethyl-imidazolidine-2,4-dione dissolved in 65 ml THF were added at −75° over 1 h and after additional stirring at −75° for 1 h, 50 ml conc. H2SO4 were added over 15 minutes. The reaction mixture was refluxed for 3 h, cooled down to r.t. and hydrolyzed with 300 ml deionized water. The organic layer was separated, washed with 10% brine and dried over Na2SO4. Filtration and evaporation of the solvent afforded 96.5 g crude 3-(4-cyclopentylmethyl-3-hydroxy-5-oxo-tetrahydro-furan-3-ylmethyl)-(1,5,5-trimethyl-imidazolidine-2,4-dione as a yellow oil, which was used without purification for the next step. 3-Cyclopentyl-propionic acid methylester was prepared from the corresponding acid (ACROS No. 11161). The methylester is also available at Chemische Fabrik K. Bucher. cooled down to −75° were added at −75° over 1 h were added at −75° over 1 h after additional stirring at −75° for 1 h The reaction mixture was refluxed for 3 h The organic layer was separated washed with 10% brine dried over Na2SO4 Filtration and evaporation of the solvent

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

実験手順: 203 ml 1.6M Butyllithium in hexane were added to a solution of 46.0 ml diisopropylamine in 120 ml THF at 0° over 1 h. The resultant LDA-solution was stirred at 0° for 1 h and then cooled down to −75°. 50.8 g 3-cyclopentyl-propionic acid methylester dissolved in 65 ml THF were added at −75° over 1 h and stirring at that temperature was continued for 1 h. 67.6 g 3-(3-tert-butoxy-2-oxo-propyl)-1,5,5-trimethyl-imidazolidine-2,4-dione dissolved in 65 ml THF were added at −75° over 1 h and after additional stirring at −75° for 1 h, 50 ml conc. H2SO4 were added over 15 minutes. The reaction mixture was refluxed for 3 h, cooled down to r.t. and hydrolyzed with 300 ml deionized water. The organic layer was separated, washed with 10% brine and dried over Na2SO4. Filtration and evaporation of the solvent afforded 96.5 g crude 3-(4-cyclopentylmethyl-3-hydroxy-5-oxo-tetrahydro-furan-3-ylmethyl)-(1,5,5-trimethyl-imidazolidine-2,4-dione as a yellow oil, which was used without purification for the next step. 3-Cyclopentyl-propionic acid methylester was prepared from the corresponding acid (ACROS No. 11161). The methylester is also available at Chemische Fabrik K. Bucher. cooled down to −75° were added at −75° over 1 h were added at −75° over 1 h after additional stirring at −75° for 1 h The reaction mixture was refluxed for 3 h The organic layer was separated washed with 10% brine dried over Na2SO4 Filtration and evaporation of the solvent

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

実験手順: To a solution of dimethyl methylphosphonate (2.17 ml, 20 mmol) in anhydrous THF (20 mL), cooled at −78° C. was added n-BuLi (1.6 M in hexane, 13.7 mL, 22 mmol). The mixture was stirred for 30 minutes at this temperature under nitrogen. Methyl 3-cyclopentylpropanoate (1.56 g, 10 mmol), prepared from 3-cyclopentylpropionic acid (Aldrich) and methanol at the presence of the catalytic amount of the concentrated sulfuric acid (the procedure described in Intermediate 17.1), was added dropwise for 10 minutes. The mixture was stirred for 2 hours at −78° C., gradually was warm to room temperature. The mixture was quenched with addition of 1N HCl to pH 4-5. The organic layer was separated, washed with brine and dried over MgSO4. The residue was purified through flash chromatography on silica gel (EtOAc:Hexanes=1:1) to give the product (1.80 g) with colorless oil in 82% yield. 1HNMR (CD3OD, ppm) δ 1.03 (m, 2H), 1.51 (m, 1H), 1.61 (m, 6H), 1.73 (m, 2H), 2.63 (t, J=7.4 Hz, 2H), 3.09 (d, J=22.7 Hz, 2H), 3.76 (s, 3H), 3.87 (s, 3H) was added dropwise for 10 minutes The mixture was stirred for 2 hours at −78° C. The mixture was quenched with addition of 1N HCl to pH 4-5 The organic layer was separated washed with brine dried over MgSO4 The residue was purified through flash chromatography on silica gel (EtOAc:Hexanes=1:1)

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

実験手順: To a solution of dimethyl methylphosphonate (2.17 ml, 20 mmol) in anhydrous THF (20 mL), cooled at −78° C. was added n-BuLi (1.6 M in hexane, 13.7 mL, 22 mmol). The mixture was stirred for 30 minutes at this temperature under nitrogen. Methyl 3-cyclopentylpropanoate (1.56 g, 10 mmol), prepared from 3-cyclopentylpropionic acid (Aldrich) and methanol at the presence of the catalytic amount of the concentrated sulfuric acid (the procedure described in Intermediate 17.1), was added dropwise for 10 minutes. The mixture was stirred for 2 hours at −78° C., gradually was warm to room temperature. The mixture was quenched with addition of 1N HCl to pH 4-5. The organic layer was separated, washed with brine and dried over MgSO4. The residue was purified through flash chromatography on silica gel (EtOAc:Hexanes=1:1) to give the product (1.80 g) with colorless oil in 82% yield. 1HNMR (CD3OD, ppm) δ 1.03 (m, 2H), 1.51 (m, 1H), 1.61 (m, 6H), 1.73 (m, 2H), 2.63 (t, J=7.4 Hz, 2H), 3.09 (d, J=22.7 Hz, 2H), 3.76 (s, 3H), 3.87 (s, 3H) was added dropwise for 10 minutes The mixture was stirred for 2 hours at −78° C. The mixture was quenched with addition of 1N HCl to pH 4-5 The organic layer was separated washed with brine dried over MgSO4 The residue was purified through flash chromatography on silica gel (EtOAc:Hexanes=1:1)

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

実験手順: 203 ml 1.6M Butyllithium in hexane were added to a solution of 46.0 ml diisopropylamine in 120 ml THF at 0° over 1 h. The resultant LDA-solution was stirred at 0° for 1 h and then cooled down to −75°. 50.8 g 3-cyclopentyl-propionic acid methylester dissolved in 65 ml THF were added at −75° over 1 h and stirring at that temperature was continued for 1 h. 67.6 g 3-(3-tert-butoxy-2-oxo-propyl)-1,5,5-trimethyl-imidazolidine-2,4-dione dissolved in 65 ml THF were added at −75° over 1 h and after additional stirring at −75° for 1 h, 50 ml conc. H2SO4 were added over 15 minutes. The reaction mixture was refluxed for 3 h, cooled down to r.t. and hydrolyzed with 300 ml deionized water. The organic layer was separated, washed with 10% brine and dried over Na2SO4. Filtration and evaporation of the solvent afforded 96.5 g crude 3-(4-cyclopentylmethyl-3-hydroxy-5-oxo-tetrahydro-furan-3-ylmethyl)-(1,5,5-trimethyl-imidazolidine-2,4-dione as a yellow oil, which was used without purification for the next step. 3-Cyclopentyl-propionic acid methylester was prepared from the corresponding acid (ACROS No. 11161). The methylester is also available at Chemische Fabrik K. Bucher. cooled down to −75° were added at −75° over 1 h were added at −75° over 1 h after additional stirring at −75° for 1 h The reaction mixture was refluxed for 3 h The organic layer was separated washed with 10% brine dried over Na2SO4 Filtration and evaporation of the solvent

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

実験手順: 203 ml 1.6M Butyllithium in hexane were added to a solution of 46.0 ml diisopropylamine in 120 ml THF at 0° over 1 h. The resultant LDA-solution was stirred at 0° for 1 h and then cooled down to −75°. 50.8 g 3-cyclopentyl-propionic acid methylester dissolved in 65 ml THF were added at −75° over 1 h and stirring at that temperature was continued for 1 h. 67.6 g 3-(3-tert-butoxy-2-oxo-propyl)-1,5,5-trimethyl-imidazolidine-2,4-dione dissolved in 65 ml THF were added at −75° over 1 h and after additional stirring at −75° for 1 h, 50 ml conc. H2SO4 were added over 15 minutes. The reaction mixture was refluxed for 3 h, cooled down to r.t. and hydrolyzed with 300 ml deionized water. The organic layer was separated, washed with 10% brine and dried over Na2SO4. Filtration and evaporation of the solvent afforded 96.5 g crude 3-(4-cyclopentylmethyl-3-hydroxy-5-oxo-tetrahydro-furan-3-ylmethyl)-(1,5,5-trimethyl-imidazolidine-2,4-dione as a yellow oil, which was used without purification for the next step. 3-Cyclopentyl-propionic acid methylester was prepared from the corresponding acid (ACROS No. 11161). The methylester is also available at Chemische Fabrik K. Bucher. cooled down to −75° were added at −75° over 1 h were added at −75° over 1 h after additional stirring at −75° for 1 h The reaction mixture was refluxed for 3 h The organic layer was separated washed with 10% brine dried over Na2SO4 Filtration and evaporation of the solvent