1-苄基-5-氧代氮杂环庚烷-4-甲酸乙酯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Commercially available 1-benzylpiperidin-4-one (78.5 g, 0.415 mol) was dissolved in tetrahydrofuran (300 mL) and the solution was cooled to −25° C. Ethyl diazoacetate (56.8 g) and boron trifluoride diethyl ether complex (128 mL) were simultaneously added dropwise to the solution over one hour, followed by stirring for one hour while elevating the temperature from −25° C. to 0° C. The reaction mixture was mixed with a saturated aqueous sodium bicarbonate solution and was extracted with ethyl acetate. The organic layer was washed with brine and was dried over anhydrous sodium sulfate. After distilling off the solvent, the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1) and thereby yielded ethyl 1-benzyl-5-oxoperhydroazepine-4-carboxylate (30.6 g, in a yield of 27%). from −25° C. to 0° C was extracted with ethyl acetate The organic layer was washed with brine was dried over anhydrous sodium sulfate After distilling off the solvent the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1)

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

实验步骤: Ethanol (50 ml) was cooled in an ice bath then sodium (442 mg, 19.2 mmol) added, with vigorous stirring. Once the sodium was dissolved, 2-phenylethanimidamide (1.29 g, 9.6 mmol) and ethyl 1-benzyl-5-oxoazepane-4-carboxylate (2.5 g, 8 mmol) was added. The reaction mixture was refluxed, under nitrogen, for 17 h. Water (10 ml) was added to quench the reaction then the reaction mixture concentrated in vacuo. The residue was partitioned between ethyl acetate (200 ml) and water (200 ml). The organic phase was dried over magnesium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel, eluting with DCM:MeOH (98:2 to 95:5), to afford a white solid, 1.35 g, 49% The reaction mixture was refluxed, under nitrogen, for 17 h to quench the reaction the reaction mixture concentrated in vacuo The residue was partitioned between ethyl acetate (200 ml) and water (200 ml) The organic phase was dried over magnesium sulphate concentrated in vacuo The residue was purified by column chromatography on silica gel eluting with DCM:MeOH (98:2 to 95:5) to afford a white solid, 1.35 g, 49%

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

实验步骤: Ethanol (30 ml) was cooled in an ice bath then sodium (160 mg, 6.70 mmol) was added, with vigorous stirring. Once the sodium was dissolved, 2-(3-chlorophenyl)ethanimidamide (474 mg, 2.81 mmol) and ethyl 1-benzyl-5-oxoazepane-4-carboxylate (876 mg, 2.81 mmol) was added. The reaction mixture was refluxed, under nitrogen, for 17 h. Water (2 ml) was added to quench the reaction then the reaction mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate (20 ml) and water (20 ml). The organic phase was dried over magnesium sulphate and concentrated in vacuo. Trituration of the residue with diethyl ether afforded the title compound as a solid in 33% yield, 361 mg. The reaction mixture was refluxed, under nitrogen, for 17 h to quench the reaction the reaction mixture was concentrated in vacuo The residue was partitioned between ethyl acetate (20 ml) and water (20 ml) The organic phase was dried over magnesium sulphate concentrated in vacuo