1,2-二甲基哌啶-4-酮

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

实验步骤: 1,2-Dimethyl-4-piperidone (1.23 g, 9.67 mmol, 1.0 equiv) was dissolved in 39 mL of 2 M NH3 in MeOH (8 equiv NH3). To this solution was added NaCN (0.52 g, 10.6 mmol, 1.1 equiv) and NH4Cl (0.57 g, 10.6 mmol, 1.1 equiv). The resulting mixture was refluxed for 2 h at which time an additional 39 mL of 2 M NH3 in MeOH was added followed by an additional 2 h of reflux. The reaction was cooled and filtered. The filtrate was concentrated and taken up in 100 mL of CH2Cl2 giving more salt precipitate which was removed by a second filtration. The filtrate was then concentrated to thick orange oil (1.32 g, 89%). 1H NMR showed a 3 to 1 mixture of diastereomers of unknown configuration. The crude product was used without further purification; MS, m/z 154=M+1. was added of reflux The reaction was cooled filtered The filtrate was concentrated was removed by a second filtration The filtrate was then concentrated to thick orange oil (1.32 g, 89%) to 1 mixture of diastereomers of unknown configuration The crude product was used without further purification

反应条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1 M solution of TiCl4 in CH2Cl2 (23 mL, 23 mmol, 1.0 equiv) was added to a flask under Ar and cooled to −15° C. with a MeOH/ice water bath. 3-[(2-Methoxycarbonyl-ethyl)-methyl-amino]-butyric acid methyl ester (5 g, 23 mmol, 1.0 equiv) was added dropwise over a 25 min period as a solution in 75 mL of dry CH2Cl2 to give a dark red mixture that was difficult to stir with a magnetic stir bar. Stirring was continued an additional 1 h and then Et3N (5.1 g, 50.6 mmol, 2.2 equiv) was added dropwise over a 30 min period and then the reaction was stirred an additional 1.5 h at −15° C. The reaction mix was poured into 150 mL of brine and 150 mL of CH2Cl2 was added. After thorough mixing, the pH of the water was brought to 8-9 with Et3N. The mix was filtered and the gel-like solid was washed 3×100 mL CH2Cl2. The filtrate layers were separated and the aqueous layer was washed 3×50 mL CH2Cl2. All of the organic layers were combined and concentrated to a thick red oil. The residue was taken up in 150 mL of concentrated HCl and the solution was refluxed 4 h. The cooled reaction solution was evaporated to dryness and the residue was dissolved in 200 mL of saturated sodium bicarbonate solution. The product ketone was extracted with 2×100 mL of EtOAc. The organic layers were combined and dried over Na2SO4. The product was purified by flash chromatography on SiO2 using pure CH2Cl2 to 4% MeOH in CH2Cl2 as eluent. The product was isolated as an orange oil (1.23 g, 42%); MS, m/z 128=M+1. to give a dark red mixture that Stirring the reaction was stirred an additional 1.5 h at −15° C The reaction mix was added The mix was filtered the gel-like solid was washed 3×100 mL CH2Cl2 The filtrate layers were separated the aqueous layer was washed 3×50 mL CH2Cl2 concentrated to a thick red oil the solution was refluxed 4 h The cooled reaction solution was evaporated to dryness the residue was dissolved in 200 mL of saturated sodium bicarbonate solution The product ketone was extracted with 2×100 mL of EtOAc dried over Na2SO4 The product was purified by flash chromatography on SiO2 using pure CH2Cl2 to 4% MeOH in CH2Cl2 as eluent

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

实验步骤: 1,2-Dimethyl-4-piperidone (1.23 g, 9.67 mmol, 1.0 equiv) was dissolved in 39 mL of 2 M NH3 in MeOH (8 equiv NH3). To this solution was added NaCN (0.52 g, 10.6 mmol, 1.1 equiv) and NH4Cl (0.57 g, 10.6 mmol, 1.1 equiv). The resulting mixture was refluxed for 2 h at which time an additional 39 mL of 2 M NH3 in MeOH was added followed by an additional 2 h of reflux. The reaction was cooled and filtered. The filtrate was concentrated and taken up in 100 mL of CH2Cl2 giving more salt precipitate which was removed by a second filtration. The filtrate was then concentrated to thick orange oil (1.32 g, 89%). 1H NMR showed a 3 to 1 mixture of diastereomers of unknown configuration. The crude product was used without further purification; MS, m/z 154=M+1. was added of reflux The reaction was cooled filtered The filtrate was concentrated was removed by a second filtration The filtrate was then concentrated to thick orange oil (1.32 g, 89%) to 1 mixture of diastereomers of unknown configuration The crude product was used without further purification

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

实验步骤: 1,2-Dimethyl-4-piperidone (1.23 g, 9.67 mmol, 1.0 equiv) was dissolved in 39 mL of 2 M NH3 in MeOH (8 equiv NH3). To this solution was added NaCN (0.52 g, 10.6 mmol, 1.1 equiv) and NH4Cl (0.57 g, 10.6 mmol, 1.1 equiv). The resulting mixture was refluxed for 2 h at which time an additional 39 mL of 2 M NH3 in MeOH was added followed by an additional 2 h of reflux. The reaction was cooled and filtered. The filtrate was concentrated and taken up in 100 mL of CH2Cl2 giving more salt precipitate which was removed by a second filtration. The filtrate was then concentrated to thick orange oil (1.32 g, 89%). 1H NMR showed a 3 to 1 mixture of diastereomers of unknown configuration. The crude product was used without further purification; MS, m/z 154=M+1. was added of reflux The reaction was cooled filtered The filtrate was concentrated was removed by a second filtration The filtrate was then concentrated to thick orange oil (1.32 g, 89%) to 1 mixture of diastereomers of unknown configuration The crude product was used without further purification

反应条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1 M solution of TiCl4 in CH2Cl2 (23 mL, 23 mmol, 1.0 equiv) was added to a flask under Ar and cooled to −15° C. with a MeOH/ice water bath. 3-[(2-Methoxycarbonyl-ethyl)-methyl-amino]-butyric acid methyl ester (5 g, 23 mmol, 1.0 equiv) was added dropwise over a 25 min period as a solution in 75 mL of dry CH2Cl2 to give a dark red mixture that was difficult to stir with a magnetic stir bar. Stirring was continued an additional 1 h and then Et3N (5.1 g, 50.6 mmol, 2.2 equiv) was added dropwise over a 30 min period and then the reaction was stirred an additional 1.5 h at −15° C. The reaction mix was poured into 150 mL of brine and 150 mL of CH2Cl2 was added. After thorough mixing, the pH of the water was brought to 8-9 with Et3N. The mix was filtered and the gel-like solid was washed 3×100 mL CH2Cl2. The filtrate layers were separated and the aqueous layer was washed 3×50 mL CH2Cl2. All of the organic layers were combined and concentrated to a thick red oil. The residue was taken up in 150 mL of concentrated HCl and the solution was refluxed 4 h. The cooled reaction solution was evaporated to dryness and the residue was dissolved in 200 mL of saturated sodium bicarbonate solution. The product ketone was extracted with 2×100 mL of EtOAc. The organic layers were combined and dried over Na2SO4. The product was purified by flash chromatography on SiO2 using pure CH2Cl2 to 4% MeOH in CH2Cl2 as eluent. The product was isolated as an orange oil (1.23 g, 42%); MS, m/z 128=M+1. to give a dark red mixture that Stirring the reaction was stirred an additional 1.5 h at −15° C The reaction mix was added The mix was filtered the gel-like solid was washed 3×100 mL CH2Cl2 The filtrate layers were separated the aqueous layer was washed 3×50 mL CH2Cl2 concentrated to a thick red oil the solution was refluxed 4 h The cooled reaction solution was evaporated to dryness the residue was dissolved in 200 mL of saturated sodium bicarbonate solution The product ketone was extracted with 2×100 mL of EtOAc dried over Na2SO4 The product was purified by flash chromatography on SiO2 using pure CH2Cl2 to 4% MeOH in CH2Cl2 as eluent

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

实验步骤: 1,2-Dimethyl-4-piperidone (1.23 g, 9.67 mmol, 1.0 equiv) was dissolved in 39 mL of 2 M NH3 in MeOH (8 equiv NH3). To this solution was added NaCN (0.52 g, 10.6 mmol, 1.1 equiv) and NH4Cl (0.57 g, 10.6 mmol, 1.1 equiv). The resulting mixture was refluxed for 2 h at which time an additional 39 mL of 2 M NH3 in MeOH was added followed by an additional 2 h of reflux. The reaction was cooled and filtered. The filtrate was concentrated and taken up in 100 mL of CH2Cl2 giving more salt precipitate which was removed by a second filtration. The filtrate was then concentrated to a thick orange oil (1.32 g, 89%). 1H NMR showed a 3 to 1 mixture of diastereomers of unknown configuration. The crude product was used without further purification; MS, m/z 154=M+1. was added of reflux The reaction was cooled filtered The filtrate was concentrated was removed by a second filtration The filtrate was then concentrated to a thick orange oil (1.32 g, 89%) to 1 mixture of diastereomers of unknown configuration The crude product was used without further purification

反应条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1 M solution of TiCl4 in CH2Cl2 (23 mL, 23 mmol, 1.0 equiv) was added to a flask under Ar and cooled to −15° C. with a MeOH/ice water bath. 3-[(2-Methoxycarbonyl-ethyl)-methyl-amino]-butyric acid methyl ester (5 g, 23 mmol, 1.0 equiv) was added dropwise over a 25 min period as solution in 75 mL of dry CH2Cl2 to give a dark red mixture that was difficult to stir with a magnetic stir bar. Stirring was continued an additional 1 h and then Et3N (5.1 g, 50.6 mmol, 2.2 equiv) was added dropwise over a 30 min period and then the reaction was stirred an additional 1.5 h at −15° C. The reaction mixture was poured into 150 mL of brine and 150 mL of CH2Cl2 was added. After thorough mixing, the pH of the water was brought to 8-9 with Et3N. The mixture was filtered and the gel-like solid was washed 3×100 mL CH2Cl2. The filtrate layers were separated and the aqueous layer was washed with 3×50 mL CH2Cl2. All of the organic layers were combined and concentrated to a thick red oil. The residue was taken up in 150 mL of concentrated HCl and the solution was refluxed 4 h. The cooled reaction solution was evaporated to dryness and the residue was dissolved in 200 mL of saturated sodium bicarbonate. The product ketone was extracted with 2×100 mL of EtOAc. The organic layers were combined and dried over Na2SO4. The product was purified by flash chromatography on SiO2 using CH2Cl2 to 4% MeOH in CH2Cl2 as eluent. The product was isolated as an orange oil (1.23 g, 42%); MS, m/z 128=M+1. to give a dark red mixture that Stirring the reaction was stirred an additional 1.5 h at −15° C was added The mixture was filtered the gel-like solid was washed 3×100 mL CH2Cl2 The filtrate layers were separated the aqueous layer was washed with 3×50 mL CH2Cl2 concentrated to a thick red oil the solution was refluxed 4 h The cooled reaction solution was evaporated to dryness the residue was dissolved in 200 mL of saturated sodium bicarbonate The product ketone was extracted with 2×100 mL of EtOAc dried over Na2SO4 The product was purified by flash chromatography on SiO2

反应条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1 M solution of TiCl4 in CH2Cl2 (23 mL, 23 mmol, 1.0 equiv) was added to a flask under Ar and cooled to −15° C. with a MeOH/ice water bath. 3-[(2-Methoxycarbonyl-ethyl)-methyl-amino]-butyric acid methyl ester (5 g, 23 mmol, 1.0 equiv) was added dropwise over a 25 min period as solution in 75 mL of dry CH2Cl2 to give a dark red mixture that was difficult to stir with a magnetic stir bar. Stirring was continued an additional 1 h and then Et3N (5.1 g, 50.6 mmol, 2.2 equiv) was added dropwise over a 30 min period and then the reaction was stirred an additional 1.5 h at −15° C. The reaction mixture was poured into 150 mL of brine and 150 mL of CH2Cl2 was added. After thorough mixing, the pH of the water was brought to 8-9 with Et3N. The mixture was filtered and the gel-like solid was washed 3×100 mL CH2Cl2. The filtrate layers were separated and the aqueous layer was washed with 3×50 mL CH2Cl2. All of the organic layers were combined and concentrated to a thick red oil. The residue was taken up in 150 mL of concentrated HCl and the solution was refluxed 4 h. The cooled reaction solution was evaporated to dryness and the residue was dissolved in 200 mL of saturated sodium bicarbonate. The product ketone was extracted with 2×100 mL of EtOAc. The organic layers were combined and dried over Na2SO4. The product was purified by flash chromatography on SiO2 using CH2Cl2 to 4% MeOH in CH2Cl2 as eluent. The product was isolated as an orange oil (1.23 g, 42%); MS, m/z 128=M+1. to give a dark red mixture that Stirring the reaction was stirred an additional 1.5 h at −15° C was added The mixture was filtered the gel-like solid was washed 3×100 mL CH2Cl2 The filtrate layers were separated the aqueous layer was washed with 3×50 mL CH2Cl2 concentrated to a thick red oil the solution was refluxed 4 h The cooled reaction solution was evaporated to dryness the residue was dissolved in 200 mL of saturated sodium bicarbonate The product ketone was extracted with 2×100 mL of EtOAc dried over Na2SO4 The product was purified by flash chromatography on SiO2

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

实验步骤: 1,2-Dimethyl-4-piperidone (1.23 g, 9.67 mmol, 1.0 equiv) was dissolved in 39 mL of 2 M NH3 in MeOH (8 equiv NH3). To this solution was added NaCN (0.52 g, 10.6 mmol, 1.1 equiv) and NH4Cl (0.57 g, 10.6 mmol, 1.1 equiv). The resulting mixture was refluxed for 2 h at which time an additional 39 mL of 2 M NH3 in MeOH was added followed by an additional 2 h of reflux. The reaction was cooled and filtered. The filtrate was concentrated and taken up in 100 mL of CH2Cl2 giving more salt precipitate which was removed by a second filtration. The filtrate was then concentrated to a thick orange oil (1.32 g, 89%). 1H NMR showed a 3 to 1 mixture of diastereomers of unknown configuration. The crude product was used without further purification; MS, m/z 154=M+1. was added of reflux The reaction was cooled filtered The filtrate was concentrated was removed by a second filtration The filtrate was then concentrated to a thick orange oil (1.32 g, 89%) to 1 mixture of diastereomers of unknown configuration The crude product was used without further purification

反应条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1 M solution of TiCl4 in CH2Cl2 (23 mL, 23 mmmol, 1.0 equiv) was added to a flask under Ar and cooled to −15° C. with a MeOH/ice water bath. 3-[(2-Methoxycarbonyl-ethyl)-methyl-amino]-butyric acid methyl ester (5 g, 23 mmol, 1.0 equiv) was added dropwise over a 25 min period as solution in 75 mL of dry CH2Cl2 to give a dark red mixture that was difficult to stir with a magnetic stir bar. Stirring was continued an additional 1 h and then Et3N (5.1 g, 50.6 mmol, 2.2 equiv) was added dropwise over a 30 min period and then the reaction was stirred an additional 1.5 h at −15° C. The reaction mixture was poured into 150 mL of brine and 150 mL of CH2Cl2 was added. After thorough mixing, the pH of the water was brought to 8-9 with Et3N. The mixture was filtered and the gel-like solid was washed 3×100 mL CH2Cl2. The filtrate layers were separated and the aqueous layer was washed with 3×50 mL CH2Cl2. All of the organic layers were combined and concentrated to a thick red oil. The residue was taken up in 150 mL of concentrated HCl and the solution was refluxed 4 h. The cooled reaction solution was evaporated to dryness and the residue was dissolved in 200 mL of saturated sodium bicarbonate. The product ketone was extracted with 2×100 mL of EtOAc. The organic layers were combined and dried over Na2SO4. The product was purified by flash chromatography on SiO2 using CH2Cl2 to 4% MeOH in CH2Cl2 as eluent. The product was isolated as an orange oil (1.23 g, 42%); MS, m/z 128=M+1. to give a dark red mixture that Stirring the reaction was stirred an additional 1.5 h at −15° C was added The mixture was filtered the gel-like solid was washed 3×100 mL CH2Cl2 The filtrate layers were separated the aqueous layer was washed with 3×50 mL CH2Cl2 concentrated to a thick red oil the solution was refluxed 4 h The cooled reaction solution was evaporated to dryness the residue was dissolved in 200 mL of saturated sodium bicarbonate The product ketone was extracted with 2×100 mL of EtOAc dried over Na2SO4 The product was purified by flash chromatography on SiO2

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

实验步骤: 1,2-Dimethyl-4-piperidone (1.23 g, 9.67 mmol, 1.0 equiv) was dissolved in 39 mL of 2 M NH3 in MeOH (8 equiv NH3). To this solution was added NaCN (0.52 g, 10.6 mmol, 1.1 equiv) and NH4Cl (0.57 g, 10.6 mmol, 1.1 equiv). The resulting mixture was refluxed for 2 h at which time an additional 39 mL of 2 M NH3 in MeOH was added followed by an additional 2 h of reflux. The reaction was cooled and filtered. The filtrate was concentrated and taken up in 100 mL of CH2Cl2 giving more salt precipitate which was removed by a second filtration. The filtrate was then concentrated to thick orange oil (1.32 g, 89%). 1H NMR showed a 3 to 1 mixture of diastereomers of unknown configuration. The crude product was used without further purification; MS, m/z 154=M+1. was added of reflux The reaction was cooled filtered The filtrate was concentrated was removed by a second filtration The filtrate was then concentrated to thick orange oil (1.32 g, 89%) to 1 mixture of diastereomers of unknown configuration The crude product was used without further purification

反应条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1 M solution of TiCl4 in CH2Cl2 (23 mL, 23 mmol, 1.0 equiv) was added to a flask under Ar and cooled to −15° C. with a MeOH/ice water bath. 3-[(2-Methoxycarbonyl-ethyl)-methyl-amino]-butyric acid methyl ester (5 g, 23 mmol, 1.0 equiv) was added dropwise over a 25 min period as a solution in 75 mL of dry CH2Cl2 to give a dark red mixture that was difficult to stir with a magnetic stir bar. Stirring was continued an additional 1 h and then Et3N (5.1 g, 50.6 mmol, 2.2 equiv) was added dropwise over a 30 min period and then the reaction was stirred an additional 1.5 h at −15° C. The reaction mix was poured into 150 mL of brine and 150 mL of CH2Cl2 was added. After thorough mixing, the pH of the water was brought to 8-9 with Et3N. The mix was filtered and the gel-like solid was washed 3×100 mL CH2Cl2. The filtrate layers were separated and the aqueous layer was washed 3×50 mL CH2Cl2. All of the organic layers were combined and concentrated to a thick red oil. The residue was taken up in 150 mL of concentrated HCl and the solution was refluxed 4 h. The cooled reaction solution was evaporated to dryness and the residue was dissolved in 200 mL of saturated sodium bicarbonate solution. The product ketone was extracted with 2×100 mL of EtOAc. The organic layers were combined and dried over Na2SO4. The product was purified by flash chromatography on SiO2 using pure CH2Cl2 to 4% MeOH in CH2Cl2 as eluent. The product was isolated as an orange oil (1.23 g, 42%); MS, m/z 128=M+1. to give a dark red mixture that Stirring the reaction was stirred an additional 1.5 h at −15° C The reaction mix was added The mix was filtered the gel-like solid was washed 3×100 mL CH2Cl2 The filtrate layers were separated the aqueous layer was washed 3×50 mL CH2Cl2 concentrated to a thick red oil the solution was refluxed 4 h The cooled reaction solution was evaporated to dryness the residue was dissolved in 200 mL of saturated sodium bicarbonate solution The product ketone was extracted with 2×100 mL of EtOAc dried over Na2SO4 The product was purified by flash chromatography on SiO2 using pure CH2Cl2 to 4% MeOH in CH2Cl2 as eluent