1-氧代-8-氮杂螺[4.5]癸烷-8-羧酸叔丁酯

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: tert-Butyl 1-oxo-8-azaspiro[4.5]decane-8-carboxylate from Procedure 1, Step G (0.526 g, 2.08 mmol) was dried by evaporating with toluene (10 mL) three times in vacuo, dissolved in methyl-tert-butyl ether (5 mL), and cooled to −78° C. To this solution was added ethyl formate (0.336 mL, 4.15 mmol) and then potassium t-butoxide (0.466 g, 4.16 mmol). After 2 days, the reaction mixture was diluted with diethyl ether, poured into 2N HCl, and extracted three times with diethyl ether. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated to afford 0.575 g. The residue was purified by flash chromatography eluting with 45% ethyl acetate/hexanes to give the title compound (0.303 g). MS/EI (acetonitrile/water): m/z 304 (M+1+Na) retention time=2.9 min. by evaporating with toluene (10 mL) three times in vacuo dissolved in methyl-tert-butyl ether (5 mL) extracted three times with diethyl ether washed with brine dried over sodium sulfate filtered concentrated to afford 0.575 g The residue was purified by flash chromatography eluting with 45% ethyl acetate/hexanes

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

实验步骤: tert-Butyl 1-oxo-8-azaspiro[4.5]decane-8-carboxylate from Procedure 1, Step G (1.2 g, 4.70 mmol) was dried by evaporating with toluene (5 mL) three times in vacuo, dissolved in tetrahydrofuran (50 mL), and cooled to −78° C. To this solution was added lithium diisopropylamide mono(tetrahydrofuran) (6.3 mL, 9.4 mmol, 1.5 M in cyclohexane). The reaction mixture was stirred for 35 min at −78° C. before adding acetaldehyde (0.527 mL, 9.4 mmol). After 10 min, the reaction mixture was diluted with diethyl ether, poured into saturated ammonium chloride, and extracted three times with diethyl ether. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated to afford 6.7 g of a clear oil. The residue was purified by flash chromatography eluting with 20–40% ethyl acetate/hexanes to give the title compound (0.620 g). by evaporating with toluene (5 mL) three times in vacuo dissolved in tetrahydrofuran (50 mL) After 10 min extracted three times with diethyl ether washed with brine dried over sodium sulfate filtered concentrated

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

实验步骤: tert-Butyl 1-oxo-8-azaspiro[4.5]decane-8-carboxylate from Step G (4.5 g, 17.8 mmol) was dried by evaporating with toluene (10 mL) three times in vacuo, dissolved in tetrahydrofuran (100 mL), and cooled to −78° C. To this solution was added lithium diisopropylamide mono(tetrahydrofuran) (24 mL, 36 mmol, 1.5 M in cyclohexane). The reaction mixture was stirred for 30 min at −78° C. before adding propionaldehyde (2.6 mL, 36 mmol). After 5 min, the reaction mixture was diluted with diethyl ether, poured into saturated ammonium chloride, and extracted three times with diethyl ether. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated to afford 6.7 g of a clear oil. The residue was purified by flash chromatography eluting with 20–30% ethyl acetate in hexanes to give the title compound (4.75 g). by evaporating with toluene (10 mL) three times in vacuo dissolved in tetrahydrofuran (100 mL) After 5 min extracted three times with diethyl ether washed with brine dried over sodium sulfate filtered concentrated

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of tert-butyl 2-(methoxycarbonyl)-1-oxo-8-azaspiro[4.5]decane-8-carboxylate (17.2 g, 0.055 mol) from Step F in a 2:2:1 mixture of ethanol/tetrahydrofuran/water (555 mL) was added pulverized lithium hydroxide (26 g, 1.10 mol). The reaction mixture was heated to 90° C. for 60 h. The reaction mixture was allowed to cool and was then concentrated, dissolved in water and dichloromethane, and extracted three times with dichloromethane. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated to afford 11.4 g. The residue was purified by flash chromatography eluting with 20–30% ethyl acetate in hexanes to give the title compound (9.41 g). was added to cool was then concentrated dissolved in water dichloromethane, and extracted three times with dichloromethane washed with brine dried over sodium sulfate filtered concentrated to afford 11.4 g The residue was purified by flash chromatography eluting with 20–30% ethyl acetate in hexanes

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: tert-Butyl 1-oxo-8-azaspiro[4.5]decane-8-carboxylate from Procedure 1, Step G (0.526 g, 2.08 mmol) was dried by evaporating with toluene (10 mL) three times in vacuo, dissolved in methyl-tert-butyl ether (5 mL), and cooled to −78° C. To this solution was added ethyl formate (0.336 mL, 4.15 mmol) and then potassium t-butoxide (0.466 g, 4.16 mmol). After 2 days, the reaction mixture was diluted with diethyl ether, poured into 2N HCl, and extracted three times with diethyl ether. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated to afford 0.575 g. The residue was purified by flash chromatography eluting with 45% ethyl acetate/hexanes to give the title compound (0.303 g). MS/EI (acetonitrile/water): m/z 304 (M+1+Na) retention time=2.9 min. by evaporating with toluene (10 mL) three times in vacuo dissolved in methyl-tert-butyl ether (5 mL) extracted three times with diethyl ether washed with brine dried over sodium sulfate filtered concentrated to afford 0.575 g The residue was purified by flash chromatography eluting with 45% ethyl acetate/hexanes

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

实验步骤: tert-Butyl 1-oxo-8-azaspiro[4.5]decane-8-carboxylate from Procedure 1, Step G (1.2 g, 4.70 mmol) was dried by evaporating with toluene (5 mL) three times in vacuo, dissolved in tetrahydrofuran (50 mL), and cooled to −78° C. To this solution was added lithium diisopropylamide mono(tetrahydrofuran) (6.3 mL, 9.4 mmol, 1.5 M in cyclohexane). The reaction mixture was stirred for 35 min at −78° C. before adding acetaldehyde (0.527 mL, 9.4 mmol). After 10 min, the reaction mixture was diluted with diethyl ether, poured into saturated ammonium chloride, and extracted three times with diethyl ether. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated to afford 6.7 g of a clear oil. The residue was purified by flash chromatography eluting with 20–40% ethyl acetate/hexanes to give the title compound (0.620 g). by evaporating with toluene (5 mL) three times in vacuo dissolved in tetrahydrofuran (50 mL) After 10 min extracted three times with diethyl ether washed with brine dried over sodium sulfate filtered concentrated

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

实验步骤: tert-Butyl 1-oxo-8-azaspiro[4.5]decane-8-carboxylate from Step G (4.5 g, 17.8 mmol) was dried by evaporating with toluene (10 mL) three times in vacuo, dissolved in tetrahydrofuran (100 mL), and cooled to −78° C. To this solution was added lithium diisopropylamide mono(tetrahydrofuran) (24 mL, 36 mmol, 1.5 M in cyclohexane). The reaction mixture was stirred for 30 min at −78° C. before adding propionaldehyde (2.6 mL, 36 mmol). After 5 min, the reaction mixture was diluted with diethyl ether, poured into saturated ammonium chloride, and extracted three times with diethyl ether. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated to afford 6.7 g of a clear oil. The residue was purified by flash chromatography eluting with 20–30% ethyl acetate in hexanes to give the title compound (4.75 g). by evaporating with toluene (10 mL) three times in vacuo dissolved in tetrahydrofuran (100 mL) After 5 min extracted three times with diethyl ether washed with brine dried over sodium sulfate filtered concentrated

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of tert-butyl 2-(methoxycarbonyl)-1-oxo-8-azaspiro[4.5]decane-8-carboxylate (17.2 g, 0.055 mol) from Step F in a 2:2:1 mixture of ethanol/tetrahydrofuran/water (555 mL) was added pulverized lithium hydroxide (26 g, 1.10 mol). The reaction mixture was heated to 90° C. for 60 h. The reaction mixture was allowed to cool and was then concentrated, dissolved in water and dichloromethane, and extracted three times with dichloromethane. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated to afford 11.4 g. The residue was purified by flash chromatography eluting with 20–30% ethyl acetate in hexanes to give the title compound (9.41 g). was added to cool was then concentrated dissolved in water dichloromethane, and extracted three times with dichloromethane washed with brine dried over sodium sulfate filtered concentrated to afford 11.4 g The residue was purified by flash chromatography eluting with 20–30% ethyl acetate in hexanes

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

实验步骤: tert-Butyl 1-oxo-8-azaspiro[4.5]decane-8-carboxylate from Procedure 1, Step G (0.526 g, 2.08 mmol) was dried by evaporating with toluene (10 mL) three times in vacuo, dissolved in methyl-tert-butyl ether (5 mL), and cooled to −78° C. To this solution was added ethyl formate (0.336 mL, 4.15 mmol) and then potassium t-butoxide (0.466 g, 4.16 mmol). After 2 days, the reaction mixture was diluted with diethyl ether, poured into 2N HCl, and extracted three times with diethyl ether. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated to afford 0.575 g. The residue was purified by flash chromatography eluting with 45% ethyl acetate/hexanes to give the title compound (0.303 g). MS/EI (acetonitrile/water): m/z 304 (M+1+Na) retention time=2.9 min. by evaporating with toluene (10 mL) three times in vacuo dissolved in methyl-tert-butyl ether (5 mL) extracted three times with diethyl ether washed with brine dried over sodium sulfate filtered concentrated to afford 0.575 g The residue was purified by flash chromatography eluting with 45% ethyl acetate/hexanes

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

实验步骤: tert-Butyl 1-oxo-8-azaspiro[4.5]decane-8-carboxylate from Procedure 1, Step G (1.2 g, 4.70 mmol) was dried by evaporating with toluene (5 mL) three times in vacuo, dissolved in tetrahydrofuran (50 mL), and cooled to −78° C. To this solution was added lithium diisopropylamide mono(tetrahydrofuran) (6.3 mL, 9.4 mmol, 1.5 M in cyclohexane). The reaction mixture was stirred for 35 min at −78° C. before adding acetaldehyde (0.527 mL, 9.4 mmol). After 10 min, the reaction mixture was diluted with diethyl ether, poured into saturated ammonium chloride, and extracted three times with diethyl ether. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated to afford 6.7 g of a clear oil. The residue was purified by flash chromatography eluting with 20–40% ethyl acetate/hexanes to give the title compound (0.620 g). by evaporating with toluene (5 mL) three times in vacuo dissolved in tetrahydrofuran (50 mL) After 10 min extracted three times with diethyl ether washed with brine dried over sodium sulfate filtered concentrated