tert-butyl (2R)-piperidine-2-carboxylate

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

実験手順: 1,4-Dichloro-7-isoquinolinylsulphonyl chloride (245 mg, 0.83 mmol) was added to a solution of tert-butyl 2(R)-piperidine carboxylate (153 mg, 0.83 mmol) and triethylamine (170 μl, 1.22 mmol) in CH2Cl2 (15 ml), and the reaction stirred at room temperature for 18 h. The solution was diluted with CH2Cl2, washed with 2M hydrochloric acid, saturated Na2CO3 solution and then brine, dried (MgSO4), and evaporated in vacuo. The residual oil was purified by column chromatography upon silica gel using an elution gradient of pentane-EtOAc (100:0 to 90:10), to give tert-butyl (2R)-1-[(1,4-dichloro-7-isoquinolinyl)sulphonyl]-2-piperidinecarboxylate, (290 mg, 0.65 mmol) as a colourless film. washed with 2M hydrochloric acid, saturated Na2CO3 solution brine, dried (MgSO4) evaporated in vacuo The residual oil was purified by column chromatography upon silica gel using an elution gradient of pentane-EtOAc (100:0 to 90:10)

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

実験手順: tert-Butyl (2R)-1-[(1,4-dichloro-7-isoquinolinyl)sulphonyl]-2-piperidinecarboxylate ##STR195## Concentrated H2SO4 (2.0 ml) was added to an ice-cold solution of 2 -(R)-piperidine carboxylic acid (415 mg, 3.21 mmol) in dioxan (10 ml). Condensed isobutylene (40 ml) was carefully added, and the reaction stirred at room temperature in a sealed vessel for 21 h. The reaction mixture was poured into an ice-cooled solution of Et2O (100 ml) and SN NaOH (20 ml), the mixture allowed to warm to room temperature with stirring, and then diluted with water. The phases were separated, the organic layer washed with 1N NaOH, then concentrated in vacuo, to half the volume, and extracted with 2N HCl. The combined acidic extracts were basified using 1N NaOH, and extracted with CH2Cl2, the combined organic solutions dried (MgSO4) and evaporated in vacuo to afford tert-butyl 2(R)-piperidine carboxylate (210 mg, 1.4 mmol) as an oil. was carefully added to warm to room temperature with stirring The phases were separated the organic layer washed with 1N NaOH concentrated in vacuo, to half the volume extracted with 2N HCl extracted with CH2Cl2 the combined organic solutions dried (MgSO4) evaporated in vacuo

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

実験手順: tert-Butyl (2R)-1-[(1,4-dichloro-7-isoquinolinyl)sulphonyl]-2-piperidinecarboxylate ##STR195## Concentrated H2SO4 (2.0 ml) was added to an ice-cold solution of 2 -(R)-piperidine carboxylic acid (415 mg, 3.21 mmol) in dioxan (10 ml). Condensed isobutylene (40 ml) was carefully added, and the reaction stirred at room temperature in a sealed vessel for 21 h. The reaction mixture was poured into an ice-cooled solution of Et2O (100 ml) and SN NaOH (20 ml), the mixture allowed to warm to room temperature with stirring, and then diluted with water. The phases were separated, the organic layer washed with 1N NaOH, then concentrated in vacuo, to half the volume, and extracted with 2N HCl. The combined acidic extracts were basified using 1N NaOH, and extracted with CH2Cl2, the combined organic solutions dried (MgSO4) and evaporated in vacuo to afford tert-butyl 2(R)-piperidine carboxylate (210 mg, 1.4 mmol) as an oil. was carefully added to warm to room temperature with stirring The phases were separated the organic layer washed with 1N NaOH concentrated in vacuo, to half the volume extracted with 2N HCl extracted with CH2Cl2 the combined organic solutions dried (MgSO4) evaporated in vacuo

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

実験手順: tert-Butyl (2R)-1-[(1,4-dichloro-7-isoquinolinyl)sulphonyl]-2-piperidinecarboxylate ##STR195## Concentrated H2SO4 (2.0 ml) was added to an ice-cold solution of 2 -(R)-piperidine carboxylic acid (415 mg, 3.21 mmol) in dioxan (10 ml). Condensed isobutylene (40 ml) was carefully added, and the reaction stirred at room temperature in a sealed vessel for 21 h. The reaction mixture was poured into an ice-cooled solution of Et2O (100 ml) and SN NaOH (20 ml), the mixture allowed to warm to room temperature with stirring, and then diluted with water. The phases were separated, the organic layer washed with 1N NaOH, then concentrated in vacuo, to half the volume, and extracted with 2N HCl. The combined acidic extracts were basified using 1N NaOH, and extracted with CH2Cl2, the combined organic solutions dried (MgSO4) and evaporated in vacuo to afford tert-butyl 2(R)-piperidine carboxylate (210 mg, 1.4 mmol) as an oil. was carefully added to warm to room temperature with stirring The phases were separated the organic layer washed with 1N NaOH concentrated in vacuo, to half the volume extracted with 2N HCl extracted with CH2Cl2 the combined organic solutions dried (MgSO4) evaporated in vacuo