ethyl 2-piperidin-4-ylideneacetate

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

実験手順: To a stirred solution of 2-(N-benzyloxycarbonyl-N-methylamino)acetaldehyde (2.07 g, 10.0 mmol) and ethyl 4-piperidinylideneacetate (1.69 g, 10.0 mmol) in MeOH—AcOH (10:1, v/v, 22 ml) was added NaBH3CN (1.32 g, 20 mmol) and the stirring was continued overnight. The mixture was quenched by addition of sat. NaHCO3 (200 ml) and extracted with CHCl3 (3×150 ml). The combined extracts were dried over MgSO4 and evaporated. The residue was chromatographed on silica-gel with CHCl3—EtOH (40:1, v/v) to give ethyl 1-[2-(N-benzyloxycarbonyl-N-methylamino)ethyl]4-piperidinylideneacetate (1.71 g, 47%) as a colorless oil. 1H-NMR (CDCl3) δ1.25 (t, J=7.3 Hz, 3 H), 2.16 (m, 2 H), 2.57 (m, 4 H), 2.95 (m, 7 H), 3.44 (m, 2 H), 4.13 (q, J=7.3 Hz, 2 H), 5.12 (s, 2 H), 5.49-5.53 (m, 1 H), 7.35 (m, 5 H). The mixture was quenched by addition of sat. NaHCO3 (200 ml) extracted with CHCl3 (3×150 ml) The combined extracts were dried over MgSO4 evaporated The residue was chromatographed on silica-gel with CHCl3—EtOH (40:1, v/v)

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

実験手順: To a stirred solution of 2-(N-benzyloxycarbonyl-N-methylamino)acetaldehyde (2.07 g, 10.0 mmol) and ethyl 4-piperidinylideneacetate (1.69 g, 10.0 mmol) in MeOH—AcOH (10:1, v/v, 22 ml) was added NaBH3CN (1.32 g, 20 mmol) and the stirring was continued overnight. The mixture was quenched by addition of sat. NaHCO3 (200 ml) and extracted with CHCl3 (3×150 ml). The combined extracts were dried over MgSO4 and evaporated. The residue was chromatographed on silica-gel with CHCl3-EtOH (40:1, v/v) to give ethyl 1-[2-(N-benzyloxycarbonyl-N-methylamino) ethyl]-4-piperidinylideneacetate (1.71 g, 47%) as a colorless oil. 1H-NMR (CDCl3) δ 1.25 (t, J=7.3 Hz, 3 H), 2.16 (m, 2 H), 2.57 (m, 4 H), 2.95 (m, 7 H), 3.44 (m, 2 H), 4.13 (q, J=7.3 Hz, 2 H), 5.12 (s, 2 H), 5.49–5.53 (m, 1 H), 7.35 (m, 5 H). The mixture was quenched by addition of sat. NaHCO3 (200 ml) extracted with CHCl3 (3×150 ml) The combined extracts were dried over MgSO4 evaporated The residue was chromatographed on silica-gel with CHCl3-EtOH (40:1, v/v)

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

実験手順: A solution of 15 ml of DIBAL (1.5 M solution in toluene) in 20 ml of toluene is added dropwise with 0.976 g of 4-(ethoxycarbonylmethylidene)piperidine, dissolved in few milliliter of toluene. The reaction mixture is stirred at room temperature for 2 hours, then it is cooled to 0-5° C. and added dropwise with methanol, until the gaz development is seen. The mixture is concentrated to a little volume and diethyl ether is added: a white solid separates, which is filtered off. The organic phase is concentrated to dryness, redissolved in diethyl ether and again filtered. The clear solution is concentrated to dryness to give 500 mg of the product. it is cooled to 0-5° C. The mixture is concentrated to a little volume and diethyl ether is added a white solid separates, which is filtered off The organic phase is concentrated to dryness redissolved in diethyl ether again filtered The clear solution is concentrated to dryness

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

実験手順: A solution of 15 ml of DIBAL (1.5 M solution in toluene) in 20 ml of toluene is added dropwise with 0.976 g of 4-(ethoxycarbonylmethylidene)piperidine, dissolved in few milliliter of toluene. The reaction mixture is stirred at room temperature for 2 hours, then it is cooled to 0-5° C. and added dropwise with methanol, until the gaz development is seen. The mixture is concentrated to a little volume and diethyl ether is added: a white solid separates, which is filtered off. The organic phase is concentrated to dryness, redissolved in diethyl ether and again filtered. The clear solution is concentrated to dryness to give 500 mg of the product. it is cooled to 0-5° C. The mixture is concentrated to a little volume and diethyl ether is added a white solid separates, which is filtered off The organic phase is concentrated to dryness redissolved in diethyl ether again filtered The clear solution is concentrated to dryness

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of sodium hydride (2.6 g) in 30 ml of tetrahydrofuran, cooled to 0° C. and kept under nitrogen atmosphere, 13 ml of triethylphosphonoacetate, dissolved in 10 ml of tetrahydrofuran are added dropwise. The temperature is then brought to room temperature and the stirring is continued for 30 minutes. The mixture is again cooled to 0° C. and it is added dropwise with a solution obtained by adding portionwise to a solution of 4-piperidone monohydrate hydrochloride (10 g) in THF 2.6 g of sodium hydride, filtered to eliminate the sodium chloride which formed. At the end of the addition, the temperature is brought to room temperature and the stirring is continued for 20 hours. The solvent is then evaporated under reduced pressure and the residue is redissolved in ethyl acetate and washed with 1 N hydrochloric acid. The aqueous phase is extracted with ethyl acetate and chloroform, then it is basified to pH=9-10 by adding 20% sodium hydroxide and it is extractedb with chloroform. The aqueous phase is then salted and extracted again with chloroform three times. The pooled extracts are dried over sodium sulfate and evaporated to give 7.1 g of the product as a yellow oil. are added dropwise is then brought to room temperature The mixture is again cooled to 0° C. it is added dropwise with a solution obtained filtered formed At the end of the addition is brought to room temperature the stirring is continued for 20 hours The solvent is then evaporated under reduced pressure the residue is redissolved in ethyl acetate washed with 1 N hydrochloric acid The aqueous phase is extracted with ethyl acetate and chloroform by adding 20% sodium hydroxide and it extracted again with chloroform three times The pooled extracts are dried over sodium sulfate evaporated

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

実験手順: To a stirred solution of 2-(N-benzyloxycarbonyl-N-methylamino)acetaldehyde (2.07 g, 10.0 mmol) and ethyl 4-piperidinylideneacetate (1.69 g, 10.0 mmol) in MeOH—AcOH (10:1, v/v, 22 ml) was added NaBH3CN (1.32 g, 20 mmol) and the stirring was continued overnight. The mixture was quenched by addition of sat. NaHCO3 (200 ml) and extracted with CHCl3 (3×150 ml). The combined extracts were dried over MgSO4 and evaporated. The residue was chromatographed on silica-gel with CHCl3—EtOH (40:1, v/v) to give ethyl 1-[2-(N-benzyloxycarbonyl-N-methylamino)ethyl]4-piperidinylideneacetate (1.71 g, 47%) as a colorless oil. 1H-NMR (CDCl3) δ1.25 (t, J=7.3 Hz, 3 H), 2.16 (m, 2 H), 2.57 (m, 4 H), 2.95 (m, 7 H), 3.44 (m, 2 H), 4.13 (q, J=7.3 Hz, 2 H), 5.12 (s, 2 H), 5.49-5.53 (m, 1 H), 7.35 (m, 5 H). The mixture was quenched by addition of sat. NaHCO3 (200 ml) extracted with CHCl3 (3×150 ml) The combined extracts were dried over MgSO4 evaporated The residue was chromatographed on silica-gel with CHCl3—EtOH (40:1, v/v)

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

実験手順: To a stirred solution of 2-(N-benzyloxycarbonyl-N-methylamino)acetaldehyde (2.07 g, 10.0 mmol) and ethyl 4-piperidinylideneacetate (1.69 g, 10.0 mmol) in MeOH—AcOH (10:1, v/v, 22 ml) was added NaBH3CN (1.32 g, 20 mmol) and the stirring was continued overnight. The mixture was quenched by addition of sat. NaHCO3 (200 ml) and extracted with CHCl3 (3×150 ml). The combined extracts were dried over MgSO4 and evaporated. The residue was chromatographed on silica-gel with CHCl3-EtOH (40:1, v/v) to give ethyl 1-[2-(N-benzyloxycarbonyl-N-methylamino) ethyl]-4-piperidinylideneacetate (1.71 g, 47%) as a colorless oil. 1H-NMR (CDCl3) δ 1.25 (t, J=7.3 Hz, 3 H), 2.16 (m, 2 H), 2.57 (m, 4 H), 2.95 (m, 7 H), 3.44 (m, 2 H), 4.13 (q, J=7.3 Hz, 2 H), 5.12 (s, 2 H), 5.49–5.53 (m, 1 H), 7.35 (m, 5 H). The mixture was quenched by addition of sat. NaHCO3 (200 ml) extracted with CHCl3 (3×150 ml) The combined extracts were dried over MgSO4 evaporated The residue was chromatographed on silica-gel with CHCl3-EtOH (40:1, v/v)

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

実験手順: To a stirred solution of 2-(N-benzyloxycarbonyl-N-methylamino)acetaldehyde (2.07 g, 10.0 mmol) and ethyl 4-piperidinylideneacetate (1.69 g, 10.0 mmol) in MeOH—AcOH (10:1, v/v, 22 ml) was added NaBH3CN (1.32 g, 20 mmol) and the stirring was continued overnight. The mixture was quenched by addition of sat. NaHCO3 (200 ml) and extracted with CHCl3 (3×150 ml). The combined extracts were dried over MgSO4 and evaporated. The residue was chromatographed on silica-gel with CHCl3-EtOH (40:1, v/v) to give ethyl 1-[2-(N-benzyloxycarbonyl-N-methylamino) ethyl]-4-piperidinylideneacetate (1.71 g, 47%) as a colorless oil. 1H-NMR (CDCl3) δ 1.25 (t, J=7.3 Hz, 3 H), 2.16 (m, 2 H), 2.57 (m, 4 H), 2.95 (m, 7 H), 3.44 (m, 2 H), 4.13 (q, J=7.3 Hz, 2 H), 5.12 (s, 2 H), 5.49–5.53 (m, 1 H), 7.35 (m, 5 H). The mixture was quenched by addition of sat. NaHCO3 (200 ml) extracted with CHCl3 (3×150 ml) The combined extracts were dried over MgSO4 evaporated The residue was chromatographed on silica-gel with CHCl3-EtOH (40:1, v/v)

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

実験手順: A solution of 15 ml of DIBAL (1.5 M solution in toluene) in 20 ml of toluene is added dropwise with 0.976 g of 4-(ethoxycarbonylmethylidene)piperidine, dissolved in few milliliter of toluene. The reaction mixture is stirred at room temperature for 2 hours, then it is cooled to 0-5° C. and added dropwise with methanol, until the gaz development is seen. The mixture is concentrated to a little volume and diethyl ether is added: a white solid separates, which is filtered off. The organic phase is concentrated to dryness, redissolved in diethyl ether and again filtered. The clear solution is concentrated to dryness to give 500 mg of the product. it is cooled to 0-5° C. The mixture is concentrated to a little volume and diethyl ether is added a white solid separates, which is filtered off The organic phase is concentrated to dryness redissolved in diethyl ether again filtered The clear solution is concentrated to dryness

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of sodium hydride (2.6 g) in 30 ml of tetrahydrofuran, cooled to 0° C. and kept under nitrogen atmosphere, 13 ml of triethylphosphonoacetate, dissolved in 10 ml of tetahydrofuran, are added dropwise. The temperature is then brought to room temperature and the stirring is continued for 30 minutes. The mixture is again cooled to 0° C. and it is added dropwise with a solution obtained by adding portionwise to a solution of 4-piperidone monohydrate hydrochloride (10 g) in THF 2.6 g of sodium hydride filtered to eliminate the sodium chloride which formed. At the end of the addition, the temperature is brought to room temperature and the stirring is continued for 20 hours. The solvent is then evaporated under reduced pressure and the residue is redissolved in ethyl acetate and washed with 1 N hydrochloric acid. The aqueous phase is extracted with ethyl acetate and chloroform, then it is basified to pH=9-10 by adding 20% sodium hydroxide and it is extracted with chloroform. The aqueous phase is then salted and extracted again with chloroform three times. The pooled extracts are dried over sodium sulfate and evaporated to give 7.1 g of the product as a yellow oil. are added dropwise is then brought to room temperature The mixture is again cooled to 0° C. it is added dropwise with a solution obtained filtered formed At the end of the addition is brought to room temperature the stirring is continued for 20 hours The solvent is then evaporated under reduced pressure the residue is redissolved in ethyl acetate washed with 1 N hydrochloric acid The aqueous phase is extracted with ethyl acetate and chloroform by adding 20% sodium hydroxide and it is extracted with chloroform extracted again with chloroform three times The pooled extracts are dried over sodium sulfate evaporated

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

実験手順: A solution of 15 ml of DIBAL (1.5 M solution in toluene) in 20 ml of toluene is added dropwise with 0.976 g of 4-(ethoxycarbonylmethylidene)piperidine, dissolved in few milliliter of toluene. The reaction mixture is stirred at room temperature for 2 hours, then it is cooled to 0-5° C. and added dropwise with methanol, until the gaz development is seen. The mixture is concentrated to a little volume and diethyl ether is added: a white solid separates, which is filtered off. The organic phase is concentrated to dryness, redissolved in diethyl ether and again filtered. The clear solution is concentrated to dryness to give 500 mg of the product. it is cooled to 0-5° C. The mixture is concentrated to a little volume and diethyl ether is added a white solid separates, which is filtered off The organic phase is concentrated to dryness redissolved in diethyl ether again filtered The clear solution is concentrated to dryness

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of sodium hydride (2.6 g) in 30 ml of tetrahydrofuran, cooled to 0° C. and kept under nitrogen atmosphere, 13 ml of triethylphosphonoacetate, dissolved in 10 ml of tetrahydrofuran are added dropwise. The temperature is then brought to room temperature and the stirring is continued for 30 minutes. The mixture is again cooled to 0° C. and it is added dropwise with a solution obtained by adding portionwise to a solution of 4-piperidone monohydrate hydrochloride (10 g) in THF 2.6 g of sodium hydride, filtered to eliminate the sodium chloride which formed. At the end of the addition, the temperature is brought to room temperature and the stirring is continued for 20 hours. The solvent is then evaporated under reduced pressure and the residue is redissolved in ethyl acetate and washed with 1 N hydrochloric acid. The aqueous phase is extracted with ethyl acetate and chloroform, then it is basified to pH=9-10 by adding 20% sodium hydroxide and it is extractedb with chloroform. The aqueous phase is then salted and extracted again with chloroform three times. The pooled extracts are dried over sodium sulfate and evaporated to give 7.1 g of the product as a yellow oil. are added dropwise is then brought to room temperature The mixture is again cooled to 0° C. it is added dropwise with a solution obtained filtered formed At the end of the addition is brought to room temperature the stirring is continued for 20 hours The solvent is then evaporated under reduced pressure the residue is redissolved in ethyl acetate washed with 1 N hydrochloric acid The aqueous phase is extracted with ethyl acetate and chloroform by adding 20% sodium hydroxide and it extracted again with chloroform three times The pooled extracts are dried over sodium sulfate evaporated