(2R)-2-甲基-2,3-二氢吡喃-4-one

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

实验步骤: Methyllithium in diethyl ether (1.6M, 218 mL, 349 mmol) was added in ˜10 mL portions over 20 min to a stirred slurry of copper(I) iodide (44.3 g, 233 mmol) in diethyl ether (350 mL) cooled to 0° C. under nitrogen. The reaction mixture was stirred at 0° C. for 30 min and then (R)-2-methyl-2H-pyran-4(3H)-one (13.5 g, 116 mmol) in diethyl ether (150 mL) was added dropwise over 30 min. The cold bath was removed and the reaction mixture was allowed to warm to rt and stirred for 3 h. The reaction mixture was slowly added (over ˜5 min) to a stirred solution of sat. NH4Cl (aq) (˜750 mL) and ice. Additional diethyl ether (˜500 mL) and water (˜150 mL) were added and the solution, which contained a grey precipitate, was stirred overnight. The layers were separated and the aqueous layer was extracted with diethyl ether (500 mL) and DCM (500 mL). The combined organic phase was dried (MgSO4), filtered and concentrated (the rotary evaporator bath temperature was held at or below ambient temperature) to an orange oil. The crude oil was purified with a Biotage® Horizon (240 g SiO2, 1-4% diethyl ether in DCM, column was pre-equilibrated with DCM) to yield (2R,6R)-2,6-dimethyldihydro-2H-pyran-4(3H)-one (13.4 g, 86% pure by 1H-NMR) as a light yellow oil. [Note: The material was carefully concentrated and contained 10% w/w DCM by 1H-NMR. 1H-NMR analysis also indicated that the material was contaminated with ˜2.5% TBDMSOH carried over from a previous reaction and 1.6% of (2R,6S)-2,6-dimethyldihydro-2H-pyran-4(3H)-one]. The analytical data of the product complied with the data reported in the literature, and the material was used without additional purification. 1H-NMR (400 MHz, CDCl3) δ 4.41-4.25 (m, 2H), 2.55 (ddd, J=14.1, 4.8, 1.4 Hz, 2H), 2.24 (ddd, J=14.1, 6.5, 1.5 Hz, 2H), 1.28 (d, J=6.5 Hz, 6H). The cold bath was removed to warm to rt stirred for 3 h The reaction mixture was slowly added (over ˜5 min) to a stirred solution of sat. NH4Cl (aq) (˜750 mL) and ice Additional diethyl ether (˜500 mL) and water (˜150 mL) were added was stirred overnight The layers were separated the aqueous layer was extracted with diethyl ether (500 mL) and DCM (500 mL) The combined organic phase was dried (MgSO4) filtered concentrated (the rotary evaporator bath temperature below ambient temperature The crude oil was purified with a Biotage® Horizon (240 g SiO2, 1-4% diethyl ether in DCM, column was pre-equilibrated with DCM)

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

实验步骤: Methyllithium in diethyl ether (1.6M, 218 mL, 349 mmol) was added in ˜10 mL portions over 20 min to a stirred slurry of copper(I) iodide (44.3 g, 233 mmol) in diethyl ether (350 mL) cooled to 0° C. under nitrogen. The reaction mixture was stirred at 0° C. for 30 min and then (R)-2-methyl-2H-pyran-4(3H)-one (13.5 g, 116 mmol) in diethyl ether (150 mL) was added dropwise over 30 min. The cold bath was removed and the reaction mixture was allowed to warm to rt and stirred for 3 h. The reaction mixture was slowly added (over ˜5 min) to a stirred solution of sat. NH4Cl (aq) (˜750 mL) and ice. Additional diethyl ether (˜500 mL) and water (˜150 mL) were added and the solution, which contained a grey precipitate, was stirred overnight. The layers were separated and the aqueous layer was extracted with diethyl ether (500 mL) and DCM (500 mL). The combined organic phase was dried (MgSO4), filtered and concentrated (the rotary evaporator bath temperature was held at or below ambient temperature) to an orange oil. The crude oil was purified with a Biotage® Horizon (240 g SiO2, 1-4% diethyl ether in DCM, column was pre-equilibrated with DCM) to yield (2R,6R)-2,6-dimethyldihydro-2H-pyran-4(3H)-one (13.4 g, 86% pure by 1H-NMR) as a light yellow oil. [Note: The material was carefully concentrated and contained 10% w/w DCM by 1H-NMR. 1H-NMR analysis also indicated that the material was contaminated with ˜2.5% TBDMSOH carried over from a previous reaction and 1.6% of (2R,6S)-2,6-dimethyldihydro-2H-pyran-4(3H)-one]. The analytical data of the product complied with the data reported in the literature, and the material was used without additional purification. 1H-NMR (400 MHz, CDCl3) δ 4.41-4.25 (m, 2H), 2.55 (ddd, J=14.1, 4.8, 1.4 Hz, 2H), 2.24 (ddd, J=14.1, 6.5, 1.5 Hz, 2H), 1.28 (d, J=6.5 Hz, 6H). The cold bath was removed to warm to rt stirred for 3 h The reaction mixture was slowly added (over ˜5 min) to a stirred solution of sat. NH4Cl (aq) (˜750 mL) and ice Additional diethyl ether (˜500 mL) and water (˜150 mL) were added was stirred overnight The layers were separated the aqueous layer was extracted with diethyl ether (500 mL) and DCM (500 mL) The combined organic phase was dried (MgSO4) filtered concentrated (the rotary evaporator bath temperature below ambient temperature The crude oil was purified with a Biotage® Horizon (240 g SiO2, 1-4% diethyl ether in DCM, column was pre-equilibrated with DCM)

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

实验步骤: Methyllithium in diethyl ether (1.6M, 218 mL, 349 mmol) was added in ˜10 mL portions over 20 min to a stirred slurry of copper(I) iodide (44.3 g, 233 mmol) in diethyl ether (350 mL) cooled to 0° C. under nitrogen. The reaction mixture was stirred at 0° C. for 30 min and then (R)-2-methyl-2H-pyran-4(3H)-one (13.5 g, 116 mmol) in diethyl ether (150 mL) was added dropwise over 30 min. The cold bath was removed and the reaction mixture was allowed to warm to rt and stirred for 3 h. The reaction mixture was slowly added (over ˜5 min) to a stirred solution of sat. NH4Cl (aq) (˜750 mL) and ice. Additional diethyl ether (˜500 mL) and water (˜150 mL) were added and the solution, which contained a grey precipitate, was stirred overnight. The layers were separated and the aqueous layer was extracted with diethyl ether (500 mL) and DCM (500 mL). The combined organic phase was dried (MgSO4), filtered and concentrated (the rotary evaporator bath temperature was held at or below ambient temperature) to an orange oil. The crude oil was purified with a Biotage® Horizon (240 g SiO2, 1-4% diethyl ether in DCM, column was pre-equilibrated with DCM) to yield (2R,6R)-2,6-dimethyldihydro-2H-pyran-4(3H)-one (13.4 g, 86% pure by 1H-NMR) as a light yellow oil. [Note: The material was carefully concentrated and contained 10% w/w DCM by 1H-NMR. 1H-NMR analysis also indicated that the material was contaminated with ˜2.5% TBDMSOH carried over from a previous reaction and 1.6% of (2R,6S)-2,6-dimethyldihydro-2H-pyran-4(3H)-one]. The analytical data of the product complied with the data reported in the literature, and the material was used without additional purification. 1H-NMR (400 MHz, CDCl3) δ 4.41-4.25 (m, 2H), 2.55 (ddd, J=14.1, 4.8, 1.4 Hz, 2H), 2.24 (ddd, J=14.1, 6.5, 1.5 Hz, 2H), 1.28 (d, J=6.5 Hz, 6H). The cold bath was removed to warm to rt stirred for 3 h The reaction mixture was slowly added (over ˜5 min) to a stirred solution of sat. NH4Cl (aq) (˜750 mL) and ice Additional diethyl ether (˜500 mL) and water (˜150 mL) were added was stirred overnight The layers were separated the aqueous layer was extracted with diethyl ether (500 mL) and DCM (500 mL) The combined organic phase was dried (MgSO4) filtered concentrated (the rotary evaporator bath temperature below ambient temperature The crude oil was purified with a Biotage® Horizon (240 g SiO2, 1-4% diethyl ether in DCM, column was pre-equilibrated with DCM)

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

实验步骤: Methyllithium in diethyl ether (1.6M, 218 mL, 349 mmol) was added in ˜10 mL portions over 20 min to a stirred slurry of copper(I) iodide (44.3 g, 233 mmol) in diethyl ether (350 mL) cooled to 0° C. under nitrogen. The reaction mixture was stirred at 0° C. for 30 min and then (R)-2-methyl-2H-pyran-4(3H)-one (13.5 g, 116 mmol) in diethyl ether (150 mL) was added dropwise over 30 min. The cold bath was removed and the reaction mixture was allowed to warm to rt and stirred for 3 h. The reaction mixture was slowly added (over ˜5 min) to a stirred solution of sat. NH4Cl (aq) (˜750 mL) and ice. Additional diethyl ether (˜500 mL) and water (˜150 mL) were added and the solution, which contained a grey precipitate, was stirred overnight. The layers were separated and the aqueous layer was extracted with diethyl ether (500 mL) and DCM (500 mL). The combined organic phase was dried (MgSO4), filtered and concentrated (the rotary evaporator bath temperature was held at or below ambient temperature) to an orange oil. The crude oil was purified with a Biotage® Horizon (240 g SiO2, 1-4% diethyl ether in DCM, column was pre-equilibrated with DCM) to yield (2R,6R)-2,6-dimethyldihydro-2H-pyran-4(3H)-one (13.4 g, 86% pure by 1H-NMR) as a light yellow oil. [Note: The material was carefully concentrated and contained 10% w/w DCM by 1H-NMR. 1H-NMR analysis also indicated that the material was contaminated with ˜2.5% TBDMSOH carried over from a previous reaction and 1.6% of (2R,6S)-2,6-dimethyldihydro-2H-pyran-4(3H)-one]. The analytical data of the product complied with the data reported in the literature, and the material was used without additional purification. 1H-NMR (400 MHz, CDCl3) δ 4.41-4.25 (m, 2H), 2.55 (ddd, J=14.1, 4.8, 1.4 Hz, 2H), 2.24 (ddd, J=14.1, 6.5, 1.5 Hz, 2H), 1.28 (d, J=6.5 Hz, 6H). The cold bath was removed to warm to rt stirred for 3 h The reaction mixture was slowly added (over ˜5 min) to a stirred solution of sat. NH4Cl (aq) (˜750 mL) and ice Additional diethyl ether (˜500 mL) and water (˜150 mL) were added was stirred overnight The layers were separated the aqueous layer was extracted with diethyl ether (500 mL) and DCM (500 mL) The combined organic phase was dried (MgSO4) filtered concentrated (the rotary evaporator bath temperature below ambient temperature The crude oil was purified with a Biotage® Horizon (240 g SiO2, 1-4% diethyl ether in DCM, column was pre-equilibrated with DCM)

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

实验步骤: Methyllithium in diethyl ether (1.6M, 218 mL, 349 mmol) was added in ˜10 mL portions over 20 min to a stirred slurry of copper(I) iodide (44.3 g, 233 mmol) in diethyl ether (350 mL) cooled to 0° C. under nitrogen. The reaction mixture was stirred at 0° C. for 30 min and then (R)-2-methyl-2H-pyran-4(3H)-one (13.5 g, 116 mmol) in diethyl ether (150 mL) was added dropwise over 30 min. The cold bath was removed and the reaction mixture was allowed to warm to rt and stirred for 3 h. The reaction mixture was slowly added (over ˜5 min) to a stirred solution of sat. NH4Cl (aq) (˜750 mL) and ice. Additional diethyl ether (˜500 mL) and water (˜150 mL) were added and the solution, which contained a grey precipitate, was stirred overnight. The layers were separated and the aqueous layer was extracted with diethyl ether (500 mL) and DCM (500 mL). The combined organic phase was dried (MgSO4), filtered and concentrated (the rotary evaporator bath temperature was held at or below ambient temperature) to an orange oil. The crude oil was purified with a Biotage® Horizon (240 g SiO2, 1-4% diethyl ether in DCM, column was pre-equilibrated with DCM) to yield (2R,6R)-2,6-dimethyldihydro-2H-pyran-4(3H)-one (13.4 g, 86% pure by 1H-NMR) as a light yellow oil. [Note: The material was carefully concentrated and contained 10% w/w DCM by 1H-NMR. 1H-NMR analysis also indicated that the material was contaminated with ˜2.5% TBDMSOH carried over from a previous reaction and 1.6% of (2R,6S)-2,6-dimethyldihydro-2H-pyran-4(3H)-one]. The analytical data of the product complied with the data reported in the literature, and the material was used without additional purification. 1H-NMR (400 MHz, CDCl3) δ 4.41-4.25 (m, 2H), 2.55 (ddd, J=14.1, 4.8, 1.4 Hz, 2H), 2.24 (ddd, J=14.1, 6.5, 1.5 Hz, 2H), 1.28 (d, J=6.5 Hz, 6H). The cold bath was removed to warm to rt stirred for 3 h The reaction mixture was slowly added (over ˜5 min) to a stirred solution of sat. NH4Cl (aq) (˜750 mL) and ice Additional diethyl ether (˜500 mL) and water (˜150 mL) were added was stirred overnight The layers were separated the aqueous layer was extracted with diethyl ether (500 mL) and DCM (500 mL) The combined organic phase was dried (MgSO4) filtered concentrated (the rotary evaporator bath temperature below ambient temperature The crude oil was purified with a Biotage® Horizon (240 g SiO2, 1-4% diethyl ether in DCM, column was pre-equilibrated with DCM)