乙基 2-氧代哌啶-4-羧酸乙酯

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

实验步骤: Ethyl 2-oxopiperidine-4-carboxylate (0.50 g, 2.9 mmol), iodobenzene (0.77 g, 3.8 mmol, 1.3 equiv), copper(I) iodide (56 mg, 0.29 mmol, 0.1 equiv), 4,7-bis(methoxy)-1,10-phenanthroline (70 mg, 0109 mmol, 0.1 equiv) and potassium carbonate (0.40 g, 3.8 mmol, 1 equiv) were combined in dimethylsulfoxide (10 mL) and placed into a preheated oil bath at 100° C. for 120 hours. The mixture was cooled to ambient temperature, diluted with ethyl acetate (50 mL) and washed with water (2×25 mL) and once with brine (25 mL). The organic extract was dried with sodium sulfate, filtered and concentrated in vacuo, providing the titled compound. washed with water (2×25 mL) and once with brine (25 mL) The organic extract was dried with sodium sulfate filtered concentrated in vacuo

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

实验步骤: Ethyl 2-oxopiperidine-4-carboxylate (0.50 g, 2.9 mmol), iodobenzene (0.77 g, 3.8 mmol, 1.3 equiv), copper(I) iodide (56 mg, 0.29 mmol, 0.1 equiv), 4,7-bis(methoxy)-1,10-phenanthroline (70 mg, 0109 mmol, 0.1 equiv) and potassium carbonate (0.40 g, 3.8 mmol, 1 equiv) were combined in dimethylsulfoxide (10 mL) and placed into a preheated oil bath at 100° C. for 120 hours. The mixture was cooled to ambient temperature, diluted with ethyl acetate (50 mL) and washed with water (2×25 mL) and once with brine (25 mL). The organic extract was dried with sodium sulfate, filtered and concentrated in vacuo, providing the titled compound. washed with water (2×25 mL) and once with brine (25 mL) The organic extract was dried with sodium sulfate filtered concentrated in vacuo

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

实验步骤: Ethyl 2-oxopiperidine-4-carboxylate (0.50 g, 2.9 mmol), iodobenzene (0.77 g, 3.8 mmol, 1.3 equiv), copper(I) iodide (56 mg, 0.29 mmol, 0.1 equiv), 4,7-bis(methoxy)-1,10-phenanthroline (70 mg, 0109 mmol, 0.1 equiv) and potassium carbonate (0.40 g, 3.8 mmol, 1 equiv) were combined in dimethylsulfoxide (10 mL) and placed into a preheated oil bath at 100° C. for 120 hours. The mixture was cooled to ambient temperature, diluted with ethyl acetate (50 mL) and washed with water (2×25 mL) and once with brine (25 mL). The organic extract was dried with sodium sulfate, filtered and concentrated in vacuo, providing the titled compound. washed with water (2×25 mL) and once with brine (25 mL) The organic extract was dried with sodium sulfate filtered concentrated in vacuo

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

实验步骤: To a solution of ethyl 2-oxopiperidine-4-carboxylate (10.76 g, 62.85 mmol) in toluene (120 mL) was added the Lawesson's reagent (25.42 g, 62.85 mmol) under a nitrogen atmosphere. The mixture was heated to reflux for 2 h. Removed the solvent under reduced pressure and the residue was purified by silica gel column chromatography (DCM/EA=20/1) to afford ethyl 2-thioxopiperidine-4-carboxylate (5.8 g, yield 49.3%). The mixture was heated to reflux for 2 h Removed the solvent under reduced pressure the residue was purified by silica gel column chromatography (DCM/EA=20/1)

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

实验步骤: To a solution of the 1-tert-butyl 4-ethyl 2-oxopiperidine-1,4-dicarboxylate (20 g, 74.45 mmol) in DCM (93 mL) was add 4N hydrogen chloride in dioxane (30 mL). The reaction was stirred at room temperature for 1 hour and then the solvent was removed under reduced pressure. The resulting residue was dissolved in DCM and water, then adjusted to PH=8 with saturated aqueous Na2CO3 solution. The mixture was extracted with DCM and the combined organic layer was washed with water, brine and dried over anhydrous Na2SO4. The organic layer was concentrated in vacuo to afford ethyl 2-oxopiperidine-4-carboxylate (12 g, yield 94.5%). the solvent was removed under reduced pressure The resulting residue was dissolved in DCM The mixture was extracted with DCM the combined organic layer was washed with water, brine dried over anhydrous Na2SO4 The organic layer was concentrated in vacuo

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

实验步骤: To a solution of ethyl 2-oxopiperidine-4-carboxylate (10.76 g, 62.85 mmol) in toluene (120 mL) was added the Lawesson's reagent (25.42 g, 62.85 mmol) under a nitrogen atmosphere. The mixture was heated to reflux for 2 h. Removed the solvent under reduced pressure and the residue was purified by silica gel column chromatography (DCM/EA=20/1) to afford ethyl 2-thioxopiperidine-4-carboxylate (5.8 g, yield 49.3%). The mixture was heated to reflux for 2 h Removed the solvent under reduced pressure the residue was purified by silica gel column chromatography (DCM/EA=20/1)

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

实验步骤: To a solution of the 1-tert-butyl 4-ethyl 2-oxopiperidine-1,4-dicarboxylate (20 g, 74.45 mmol) in DCM (93 mL) was add 4N hydrogen chloride in dioxane (30 mL). The reaction was stirred at room temperature for 1 hour and then the solvent was removed under reduced pressure. The resulting residue was dissolved in DCM and water, then adjusted to PH=8 with saturated aqueous Na2CO3 solution. The mixture was extracted with DCM and the combined organic layer was washed with water, brine and dried over anhydrous Na2SO4. The organic layer was concentrated in vacuo to afford ethyl 2-oxopiperidine-4-carboxylate (12 g, yield 94.5%). the solvent was removed under reduced pressure The resulting residue was dissolved in DCM The mixture was extracted with DCM the combined organic layer was washed with water, brine dried over anhydrous Na2SO4 The organic layer was concentrated in vacuo

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

实验步骤: Add trimethyloxonium tetrafluoroborate (530.7 g) to a solution of 2-oxopiperidine-4-carboxylic acid ethyl ester (307.7 g, 1.80 mol) in dry dichloromethane (4.68 L) under nitrogen, and stir the reaction at room temperature for 16 hours. Cool the mixture to 0° C. and adjust to pH 8 with saturated aqueous sodium bicarbonate. Separate the layers and extract the aqueous phase with additional dichloromethane (2×1 L). Combine the organic phases, dry over magnesium sulfate, filter, and concentrate to provide the title compound (273.68 g). Mass spectrum (m/z): 186 (M+1). the reaction at room temperature for 16 hours Separate the layers extract the aqueous phase with additional dichloromethane (2×1 L) Combine the organic phases, dry over magnesium sulfate filter concentrate

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

实验步骤: Add 2-oxopiperidine-4-carboxylic acid ethyl ester (6.0 g, 35 mmol) to a solution of trimethyloxonium tetrafluoroborate (9.0 g, 59.6 mmol) in dichloromethane (78 mL) cooled to 0° C. Stir the reaction for 3 hours and pour into an ice cold solution of saturated aqueous sodium bicarbonate. Separate layers and extract the aqueous layer with additional dichloromethane. Combine the organic layers, dry over anhydrous sodium sulfate, filter, and concentrate under reduced pressure to afford the title compound which was used without further purification (5.87 g, 90%). Mass spectrum (m/z): 186 (M+1). the reaction for 3 hours Separate layers and extract the aqueous layer with additional dichloromethane dry over anhydrous sodium sulfate filter concentrate under reduced pressure

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

实验步骤: Ethyl 2-oxopiperidine-4-carboxylate (0.50 g, 2.9 mmol), iodobenzene (0.77 g, 3.8 mmol, 1.3 equiv), copper(I) iodide (56 mg, 0.29 mmol, 0.1 equiv), 4,7-bis(methoxy)-1,10-phenanthroline (70 mg, 0109 mmol, 0.1 equiv) and potassium carbonate (0.40 g, 3.8 mmol, 1 equiv) were combined in dimethylsulfoxide (10 mL) and placed into a preheated oil bath at 100° C. for 120 hours. The mixture was cooled to ambient temperature, diluted with ethyl acetate (50 mL) and washed with water (2×25 mL) and once with brine (25 mL). The organic extract was dried with sodium sulfate, filtered and concentrated in vacuo, providing the titled compound. washed with water (2×25 mL) and once with brine (25 mL) The organic extract was dried with sodium sulfate filtered concentrated in vacuo

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

实验步骤: To a solution of ethyl 2-oxopiperidine-4-carboxylate (10.76 g, 62.85 mmol) in toluene (120 mL) was added the Lawesson's reagent (25.42 g, 62.85 mmol) under a nitrogen atmosphere. The mixture was heated to reflux for 2 h. Removed the solvent under reduced pressure and the residue was purified by silica gel column chromatography (DCM/EA=20/1) to afford ethyl 2-thioxopiperidine-4-carboxylate (5.8 g, yield 49.3%). The mixture was heated to reflux for 2 h Removed the solvent under reduced pressure the residue was purified by silica gel column chromatography (DCM/EA=20/1)

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

实验步骤: To a solution of the 1-tert-butyl 4-ethyl 2-oxopiperidine-1,4-dicarboxylate (20 g, 74.45 mmol) in DCM (93 mL) was add 4N hydrogen chloride in dioxane (30 mL). The reaction was stirred at room temperature for 1 hour and then the solvent was removed under reduced pressure. The resulting residue was dissolved in DCM and water, then adjusted to PH=8 with saturated aqueous Na2CO3 solution. The mixture was extracted with DCM and the combined organic layer was washed with water, brine and dried over anhydrous Na2SO4. The organic layer was concentrated in vacuo to afford ethyl 2-oxopiperidine-4-carboxylate (12 g, yield 94.5%). the solvent was removed under reduced pressure The resulting residue was dissolved in DCM The mixture was extracted with DCM the combined organic layer was washed with water, brine dried over anhydrous Na2SO4 The organic layer was concentrated in vacuo