ethyl 2-methyl-2-(oxan-4-yl)propanoate

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1 g (tetrahydro-pyran-4-yl)-acetic acid ethyl ester [103260-44-2] in 3 ml of dry tetrahydrofuran is added dropwise to a solution of lithium diisopropyl amide (freshly prepared from 1 ml diisopropyl amine and 4.3 ml 1.6 M butyllithium solution in hexanes) in 5 ml of dry tetrahydrofuran at −78° C. The reaction mixture is stirred for 15 minutes at −78° C. and then 0.46 ml of methyl iodide are added and the mixture is allowed to warm to 0° C. over a period of 15 minutes. The reaction mixture is re-cooled to −78° C. and then a solution of lithium diisopropyl amide (freshly prepared from 1 ml diisopropyl amine and 4.3 ml 1.6 M butyllithium solution in hexanes) in 5 ml of dry tetrahydrofuran is added dropwise. The solution is stirred for 15 minutes at −78° C. and then 0.46 ml of methyl iodide are added and the mixture is allowed to warm to room temperature. After 2 hours, the reaction mixture is quenched with 20 ml of 1M HCl and then extracted with tert-butyl methyl ether (2×). The combined organic phases are washed with brine, dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a colourless oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.27 (1:5 EtOAc-heptane). to warm to 0° C. over a period of 15 minutes The reaction mixture is re-cooled to −78° C. is added dropwise The solution is stirred for 15 minutes at −78° C. to warm to room temperature After 2 hours the reaction mixture is quenched with 20 ml of 1M HCl extracted with tert-butyl methyl ether (2×) The combined organic phases are washed with brine dried over sodium sulphate concentrated by evaporation

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1 g (tetrahydro-pyran-4-yl)-acetic acid ethyl ester [103260-44-2] in 3 ml of dry tetrahydrofuran is added dropwise to a solution of lithium diisopropyl amide (freshly prepared from 1 ml diisopropyl amine and 4.3 ml 1.6 M butyllithium solution in hexanes) in 5 ml of dry tetrahydrofuran at −78° C. The reaction mixture is stirred for 15 minutes at −78° C. and then 0.46 ml of methyl iodide are added and the mixture is allowed to warm to 0° C. over a period of 15 minutes. The reaction mixture is re-cooled to −78° C. and then a solution of lithium diisopropyl amide (freshly prepared from 1 ml diisopropyl amine and 4.3 ml 1.6 M butyllithium solution in hexanes) in 5 ml of dry tetrahydrofuran is added dropwise. The solution is stirred for 15 minutes at −78° C. and then 0.46 ml of methyl iodide are added and the mixture is allowed to warm to room temperature. After 2 hours, the reaction mixture is quenched with 20 ml of 1M HCl and then extracted with tert-butyl methyl ether (2×). The combined organic phases are washed with brine, dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a colourless oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.27 (1:5 EtOAc-heptane). to warm to 0° C. over a period of 15 minutes The reaction mixture is re-cooled to −78° C. is added dropwise The solution is stirred for 15 minutes at −78° C. to warm to room temperature After 2 hours the reaction mixture is quenched with 20 ml of 1M HCl extracted with tert-butyl methyl ether (2×) The combined organic phases are washed with brine dried over sodium sulphate concentrated by evaporation

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

実験手順: A solution of 0.795 g of 2-methyl-2-(tetrahydro-pyran-4-yl)-propionic acid ethyl ester in 3 ml of ethanol is admixed with 3 ml of a 40% aqueous potassium hydroxide solution and then heated to reflux. After 4 hours, the reaction mixture is cooled to room temperature and the ethanol removed in vacuo. The remaining aqueous solution is acidified (pH 2-3) with 4M HCl and then extracted with tert-butyl methyl ether (2×). The combined organic layers are washed with water and brine, dried over sodium sulphate and concentrated by evaporation to provide the crude title compound as a yellow solid. Rf=0.10 (1:3 EtOAc-heptane). heated to reflux the ethanol removed in vacuo extracted with tert-butyl methyl ether (2×) The combined organic layers are washed with water and brine dried over sodium sulphate concentrated by evaporation

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

実験手順: A solution of 0.795 g of 2-methyl-2-(tetrahydro-pyran-4-yl)-propionic acid ethyl ester in 3 ml of ethanol is admixed with 3 ml of a 40% aqueous potassium hydroxide solution and then heated to reflux. After 4 hours, the reaction mixture is cooled to room temperature and the ethanol removed in vacuo. The remaining aqueous solution is acidified (pH 2-3) with 4M HCl and then extracted with tert-butyl methyl ether (2×). The combined organic layers are washed with water and brine, dried over sodium sulphate and concentrated by evaporation to provide the crude title compound as a yellow solid. Rf=0.10 (1:3 EtOAc-heptane). heated to reflux the ethanol removed in vacuo extracted with tert-butyl methyl ether (2×) The combined organic layers are washed with water and brine dried over sodium sulphate concentrated by evaporation

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1 g (tetrahydro-pyran-4-yl)-acetic acid ethyl ester [103260-44-2] in 3 ml of dry tetrahydrofuran is added dropwise to a solution of lithium diisopropyl amide (freshly prepared from 1 ml diisopropyl amine and 4.3 ml 1.6 M butyllithium solution in hexanes) in 5 ml of dry tetrahydrofuran at −78° C. The reaction mixture is stirred for 15 minutes at −78° C. and then 0.46 ml of methyl iodide are added and the mixture is allowed to warm to 0° C. over a period of 15 minutes. The reaction mixture is re-cooled to −78° C. and then a solution of lithium diisopropyl amide (freshly prepared from 1 ml diisopropyl amine and 4.3 ml 1.6 M butyllithium solution in hexanes) in 5 ml of dry tetrahydrofuran is added dropwise. The solution is stirred for 15 minutes at −78° C. and then 0.46 ml of methyl iodide are added and the mixture is allowed to warm to room temperature. After 2 hours, the reaction mixture is quenched with 20 ml of 1M HCl and then extracted with tert-butyl methyl ether (2×). The combined organic phases are washed with brine, dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a colourless oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.27 (1:5 EtOAc-heptane). to warm to 0° C. over a period of 15 minutes The reaction mixture is re-cooled to −78° C. is added dropwise The solution is stirred for 15 minutes at −78° C. to warm to room temperature After 2 hours the reaction mixture is quenched with 20 ml of 1M HCl extracted with tert-butyl methyl ether (2×) The combined organic phases are washed with brine dried over sodium sulphate concentrated by evaporation

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

実験手順: A solution of 0.795 g of 2-methyl-2-(tetrahydro-pyran-4-yl)-propionic acid ethyl ester in 3 ml of ethanol is admixed with 3 ml of a 40% aqueous potassium hydroxide solution and then heated to reflux. After 4 hours, the reaction mixture is cooled to room temperature and the ethanol removed in vacuo. The remaining aqueous solution is acidified (pH 2-3) with 4M HCl and then extracted with tert-butyl methyl ether (2×). The combined organic layers are washed with water and brine, dried over sodium sulphate and concentrated by evaporation to provide the crude title compound as a yellow solid. Rf=0.10 (1:3 EtOAc-heptane). heated to reflux the ethanol removed in vacuo extracted with tert-butyl methyl ether (2×) The combined organic layers are washed with water and brine dried over sodium sulphate concentrated by evaporation

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1 g (tetrahydro-pyran-4-yl)-acetic acid ethyl ester [103260-44-2] in 3 ml of dry tetrahydrofuran is added dropwise to a solution of lithium diisopropyl amide (freshly prepared from 1 ml diisopropyl amine and 4.3 ml 1.6 M butyllithium solution in hexanes) in 5 ml of dry tetrahydrofuran at −78° C. The reaction mixture is stirred for 15 minutes at −78° C. and then 0.46 ml of methyl iodide are added and the mixture is allowed to warm to 0° C. over a period of 15 minutes. The reaction mixture is re-cooled to −78° C. and then a solution of lithium diisopropyl amide (freshly prepared from 1 ml diisopropyl amine and 4.3 ml 1.6 M butyllithium solution in hexanes) in 5 ml of dry tetrahydrofuran is added dropwise. The solution is stirred for 15 minutes at −78° C. and then 0.46 ml of methyl iodide are added and the mixture is allowed to warm to room temperature. After 2 hours, the reaction mixture is quenched with 20 ml of 1M HCl and then extracted with tert-butyl methyl ether (2×). The combined organic phases are washed with brine, dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a colourless oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.27 (1:5 EtOAc-heptane). to warm to 0° C. over a period of 15 minutes The reaction mixture is re-cooled to −78° C. is added dropwise The solution is stirred for 15 minutes at −78° C. to warm to room temperature After 2 hours the reaction mixture is quenched with 20 ml of 1M HCl extracted with tert-butyl methyl ether (2×) The combined organic phases are washed with brine dried over sodium sulphate concentrated by evaporation

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

実験手順: A solution of 0.795 g of 2-methyl-2-(tetrahydro-pyran-4-yl)-propionic acid ethyl ester in 3 ml of ethanol is admixed with 3 ml of a 40% aqueous potassium hydroxide solution and then heated to reflux. After 4 hours, the reaction mixture is cooled to room temperature and the ethanol removed in vacuo. The remaining aqueous solution is acidified (pH 2-3) with 4M HCl and then extracted with tert-butyl methyl ether (2×). The combined organic layers are washed with water and brine, dried over sodium sulphate and concentrated by evaporation to provide the crude title compound as a yellow solid. Rf=0.10 (1:3 EtOAc-heptane). heated to reflux the ethanol removed in vacuo extracted with tert-butyl methyl ether (2×) The combined organic layers are washed with water and brine dried over sodium sulphate concentrated by evaporation