tert-butyl 8-azaspiro[4.5]decane-8-carboxylate

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-butyl 8-azaspiro[4.5]decane-8-carboxylate (Intermediate 71, 6 g, 25.07 mmol) dissolved in 150 ml of Et2O was cooled to −78° C., then N,N,N′,N′-tetramethyl ethylendiamine (9.08 ml, 60.16 mmol) and secBuLi 1.4M in hexane (42.95 ml, 60.16 mmol) were added. After 10 minutes at −60° C., the temperature was raised to −20° C. for 60 minutes, then the reaction was cooled to −78° C. and dimethylformamide (4.47 ml, 60.16 mmol, dissolved in 5 ml of Et2O) was added. After 30 minutes a saturated aqueous solution of NH4Cl (30 ml) was slowly added, then reaction was allowed to reach room temperature. Reaction was extracted with Et2O (3×100 ml), the organic solvent was dried (Na2SO4) and evaporated to obtain 4 g of the title compound as yellow oil. the temperature was raised to −20° C. for 60 minutes the reaction was cooled to −78° C. reaction to reach room temperature Reaction was extracted with Et2O (3×100 ml) the organic solvent was dried (Na2SO4) evaporated

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

实验步骤: To a solution of 8-azaspiro[4.5]decane (which has been described in WO 9800404 A1 6.2 g, 44.5 mmol) in dichloromethane (130 ml), which was cooled to 0° C., triethylamine (7.5 ml, 53.4 mmol) was added then a solution of tert-butyl dicarbonate (10.68 g, 48.9 mmol) in dichloromethane (50 ml) was added in 20 minutes. The clear solution was maintained under stirring at room temperature for 18 hours, then dichloromethane (50 ml) was added and the organic solution was washed with water (2×20 ml), HCl 0.1N (20 ml) then water (2×20 ml). The organic solvent was anhydrified (Na2SO4) and evaporated to give a crude that was purified on silica gel column (Hexane/AcOEt 95/5) to give 6 g of the title compound (light yellow solid). The clear solution was maintained the organic solution was washed with water (2×20 ml), HCl 0.1N (20 ml) evaporated to give a crude that was purified on silica gel column (Hexane/AcOEt 95/5)

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

实验步骤: To a solution of 8-azaspiro[4.5]decane (which has been described in WO 9800404 A1 6.2 g, 44.5 mmol) in dichloromethane (130 ml), which was cooled to 0° C., triethylamine (7.5 ml, 53.4 mmol) was added then a solution of tert-butyl dicarbonate (10.68 g, 48.9 mmol) in dichloromethane (50 ml) was added in 20 minutes. The clear solution was maintained under stirring at room temperature for 18 hours, then dichloromethane (50 ml) was added and the organic solution was washed with water (2×20 ml), HCl 0.1N (20 ml) then water (2×20 ml). The organic solvent was anhydrified (Na2SO4) and evaporated to give a crude that was purified on silica gel column (Hexane/AcOEt 95/5) to give 6 g of the title compound (light yellow solid). The clear solution was maintained the organic solution was washed with water (2×20 ml), HCl 0.1N (20 ml) evaporated to give a crude that was purified on silica gel column (Hexane/AcOEt 95/5)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: tert-butyl 8-azaspiro[4.5]decane-8-carboxylate (Intermediate 71, 6 g, 25.07 mmol) dissolved in 150 ml of Et2O was cooled to −78° C., then N,N,N′,N′-tetramethyl ethylendiamine (9.08 ml, 60.16 mmol) and secBuLi 1.4M in hexane (42.95 ml, 60.16 mmol) were added. After 10 minutes at −60° C., the temperature was raised to −20° C. for 60 minutes, then the reaction was cooled to −78° C. and dimethylformamide (4.47 ml, 60.16 mmol, dissolved in 5 ml of Et2O) was added. After 30 minutes a saturated aqueous solution of NH4Cl (30 ml) was slowly added, then reaction was allowed to reach room temperature. Reaction was extracted with Et2O (3×100 ml), the organic solvent was dried (Na2SO4) and evaporated to obtain 4 g of the title compound as yellow oil. the temperature was raised to −20° C. for 60 minutes the reaction was cooled to −78° C. reaction to reach room temperature Reaction was extracted with Et2O (3×100 ml) the organic solvent was dried (Na2SO4) evaporated

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

实验步骤: To a solution of 8-azaspiro[4.5]decane (which has been described in WO 9800404 A1 6.2 g, 44.5 mmol) in dichloromethane (130 ml), which was cooled to 0° C., triethylamine (7.5 ml, 53.4 mmol) was added then a solution of tert-butyl dicarbonate (10.68 g, 48.9 mmol) in dichloromethane (50 ml) was added in 20 minutes. The clear solution was maintained under stirring at room temperature for 18 hours, then dichloromethane (50 ml) was added and the organic solution was washed with water (2×20 ml), HCl 0.1N (20 ml) then water (2×20 ml). The organic solvent was anhydrified (Na2SO4) and evaporated to give a crude that was purified on silica gel column (Hexane/AcOEt 95/5) to give 6 g of the title compound (light yellow solid). The clear solution was maintained the organic solution was washed with water (2×20 ml), HCl 0.1N (20 ml) evaporated to give a crude that was purified on silica gel column (Hexane/AcOEt 95/5)