乙基 2-(氧杂-2-基)乙酸甲酯

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 6.83 mmol of lithium diisopropylamide (2M in tetrahydrofuran) are added dropwise to a solution of 5.69 mmol of ethyl tetrahydropyranylacetate [103260-44-2] in 10 ml of tetrahydrofuran at −78° C. The mixture is stirred at −78° C. for 15 minutes and 7.39 mmol of dibromoethane are added. The reaction mixture is warmed to 0° C. over 15 minutes and then cooled again to −78° C. 6.83 mmol of lithium diisopropylamide (2M in tetrahydrofuran) are again added dropwise to the reaction mixture. It is warmed to room temperature over 2 hours and quenched with 1M HCl. The phases are separated and the aqueous phase is extracted with tert-butyl methyl ether (2×). The combined organic phases are washed with brine, dried with sodium sulphate and evaporated. The title compound is identified by means of the Rf from the residue by flash chromatography (SiO2 60 F). The reaction mixture is warmed to 0° C. over 15 minutes cooled again to −78° C It is warmed to room temperature over 2 hours quenched with 1M HCl The phases are separated the aqueous phase is extracted with tert-butyl methyl ether (2×) The combined organic phases are washed with brine dried with sodium sulphate evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following the procedure of Preparative Example 14, 2.0 g (17.5 mmol) of ethyl diazo acetate was reacted with tetrahydropyran to give 1.75 g of the product as a colorless oil, bp 95°-106° C. at 20 mm Hg.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following the procedure of Preparative Example 14, 2.0 g (17.5 mmol) of ethyl diazo acetate was reacted with tetrahydropyran to give 1.75 g of the product as a colorless oil, bp 95°-106° C. at 20 mm Hg.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following the procedure of Preparative Example 14, 2.0 g (17.5 mmol) of ethyl diazo acetate was reacted with tetrahydropyran to give 1.75 g of the product as a colorless oil, bp 95°-106° C. at 20 mm Hg.

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (tetrahydro-pyran-2-yl)-acetic acid ethyl ester (77.1 g, 0.45 mol) in tetrahydrofuran (1.5 L) at 0° C. was added lithium aluminium hydride (22.1 g, 0.58 mol) in several portions. The mixture was stirred at 0° C. for 2 h and quenched with 1 N sodium hydroxide solution. The mixture was filtered and the filter cake was washed with dichloromethane (4×300 mL). The combined organic layers were concentrated in vacuo. The crude product was purified by distillation under reduced pressure to afford 2-(tetrahydro-pyran-2-yl)-ethanol (53.5 g, 92% yield) as a colorless oil. quenched with 1 N sodium hydroxide solution The mixture was filtered the filter cake was washed with dichloromethane (4×300 mL) The combined organic layers were concentrated in vacuo The crude product was purified by distillation under reduced pressure

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 7-hydroxy-hept-2-enoic acid ethyl ester (99.9 g, 0.58 mol) in tetrahydrofuran prepared in the previous step, cooled with ice-water bath, was added sodium hydride (4.80 g, 0.12 mol, 60%) in two portions. The mixture was stirred at 0° C. for 2 h and then at room temperature for 2 h. The mixture was neutralized with a 1 M aqueous hydrochloric acid solution (pH ˜5.0-6.0). Water (1 L) was then added and the mixture was extracted with ethyl acetate (3×1 L). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was treated with hexanes/ethyl acetate (3×800 mL, hexanes/ethyl acetate=10/1, v/v). The mixture was filtered and dried over anhydrous sodium sulfate. The filtrate was concentrated and the crude product was purified by flash column chromatography (QingDao silica gel, 200-300 mesh, 10% ethyl acetate/hexanes) to afford (tetrahydro-pyran-2-yl)-acetic acid ethyl ester (77.1 g, 77% yield). cooled with ice-water bath at room temperature for 2 h the mixture was extracted with ethyl acetate (3×1 L) The combined organic layers were dried over anhydrous sodium sulfate concentrated in vacuo The residue was treated with hexanes/ethyl acetate (3×800 mL, hexanes/ethyl acetate=10/1 The mixture was filtered dried over anhydrous sodium sulfate The filtrate was concentrated the crude product was purified by flash column chromatography (QingDao silica gel, 200-300 mesh, 10% ethyl acetate/hexanes)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 6.83 mmol of lithium diisopropylamide (2M in tetrahydrofuran) are added dropwise to a solution of 5.69 mmol of ethyl tetrahydropyranylacetate [103260-44-2] in 10 ml of tetrahydrofuran at −78° C. The mixture is stirred at −78° C. for 15 minutes and 7.39 mmol of dibromoethane are added. The reaction mixture is warmed to 0° C. over 15 minutes and then cooled again to −78° C. 6.83 mmol of lithium diisopropylamide (2M in tetrahydrofuran) are again added dropwise to the reaction mixture. It is warmed to room temperature over 2 hours and quenched with 1M HCl. The phases are separated and the aqueous phase is extracted with tert-butyl methyl ether (2×). The combined organic phases are washed with brine, dried with sodium sulphate and evaporated. The title compound is identified by means of the Rf from the residue by flash chromatography (SiO2 60 F). The reaction mixture is warmed to 0° C. over 15 minutes cooled again to −78° C It is warmed to room temperature over 2 hours quenched with 1M HCl The phases are separated the aqueous phase is extracted with tert-butyl methyl ether (2×) The combined organic phases are washed with brine dried with sodium sulphate evaporated