tert-butyl 9-oxo-7-oxa-3,10-diazaspiro[5.6]dodecane-3-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Borane-methyl sulfide complex (2M in THF, 2.88 mL) was added to a solution of tert-butyl 9-oxo-7-oxa-3,10-diazaspiro[5.6]dodecane-3-carboxylate (example 89, step d) (0.41 g) in dry THF (40 mL) and the reaction mixture then heated at 70° C. for 30 minutes under nitrogen. The mixture was cooled to room temperature and quenched with methanol. The solvents were removed under reduced pressure and the residue dissolved in methanol (100 mL). N1,N2-dimethylethane-1,2-diamine (1.0 g) was added and the mixture heated at reflux under nitrogen for 16 h. Further N1,N2-dimethylethane-1,2-diamine (1.0 g) was added and refluxing continued for 16 h. The solvents were evaporated under reduced pressure and the residue azeotroped with toluene. The crude product was purified by flash silica chromatography using 6% methanol in dichloromethane with 1% triethylamine as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.176 g. The mixture was cooled to room temperature quenched with methanol The solvents were removed under reduced pressure the residue dissolved in methanol (100 mL) N1,N2-dimethylethane-1,2-diamine (1.0 g) was added the mixture heated at reflux under nitrogen for 16 h Further N1,N2-dimethylethane-1,2-diamine (1.0 g) was added refluxing The solvents were evaporated under reduced pressure the residue azeotroped with toluene The crude product was purified by flash silica chromatography Pure fractions were evaporated to dryness

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Borane-methyl sulfide complex (2M in THF, 2.88 mL) was added to a solution of tert-butyl 9-oxo-7-oxa-3,10-diazaspiro[5.6]dodecane-3-carboxylate (example 89, step d) (0.41 g) in dry THF (40 mL) and the reaction mixture then heated at 70° C. for 30 minutes under nitrogen. The mixture was cooled to room temperature and quenched with methanol. The solvents were removed under reduced pressure and the residue dissolved in methanol (100 mL). N1,N2-dimethylethane-1,2-diamine (1.0 g) was added and the mixture heated at reflux under nitrogen for 16 h. Further N1,N2-dimethylethane-1,2-diamine (1.0 g) was added and refluxing continued for 16 h. The solvents were evaporated under reduced pressure and the residue azeotroped with toluene. The crude product was purified by flash silica chromatography using 6% methanol in dichloromethane with 1% triethylamine as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.176 g. The mixture was cooled to room temperature quenched with methanol The solvents were removed under reduced pressure the residue dissolved in methanol (100 mL) N1,N2-dimethylethane-1,2-diamine (1.0 g) was added the mixture heated at reflux under nitrogen for 16 h Further N1,N2-dimethylethane-1,2-diamine (1.0 g) was added refluxing The solvents were evaporated under reduced pressure the residue azeotroped with toluene The crude product was purified by flash silica chromatography Pure fractions were evaporated 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 tert-butyl 4-(2-(2-chloroacetamido)ethyl)-4-hydroxypiperidine-1-carboxylate (example 89, step c) (0.3 g) in dry THF (18 mL) was added dropwise over 6 hours to a refluxing mixture of potassium tert-butoxide (1M in tert-butanol, 3 mL) and dry THF (60 mL). At the end of the addition the mixture was heated at reflux for a further 15 minutes and then cooled to room temperature. The mixture was partitioned between ethyl acetate and brine. The organic layer was dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. Tritruration with diethylether afforded the subtitled compound. Yield 0.117 g. At the end of the addition the mixture was heated at reflux for a further 15 minutes The mixture was partitioned between ethyl acetate and brine The organic layer was dried over sodium sulphate filtered the solvent evaporated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Borane-methyl sulfide complex (2M in THF, 2.88 mL) was added to a solution of tert-butyl 9-oxo-7-oxa-3,10-diazaspiro[5.6]dodecane-3-carboxylate (example 89, step d) (0.41 g) in dry THF (40 mL) and the reaction mixture then heated at 70° C. for 30 minutes under nitrogen. The mixture was cooled to room temperature and quenched with methanol. The solvents were removed under reduced pressure and the residue dissolved in methanol (100 mL). N1,N2-dimethylethane-1,2-diamine (1.0 g) was added and the mixture heated at reflux under nitrogen for 16 h. Further N1,N2-dimethylethane-1,2-diamine (1.0 g) was added and refluxing continued for 16 h. The solvents were evaporated under reduced pressure and the residue azeotroped with toluene. The crude product was purified by flash silica chromatography using 6% methanol in dichloromethane with 1% triethylamine as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.176 g. The mixture was cooled to room temperature quenched with methanol The solvents were removed under reduced pressure the residue dissolved in methanol (100 mL) N1,N2-dimethylethane-1,2-diamine (1.0 g) was added the mixture heated at reflux under nitrogen for 16 h Further N1,N2-dimethylethane-1,2-diamine (1.0 g) was added refluxing The solvents were evaporated under reduced pressure the residue azeotroped with toluene The crude product was purified by flash silica chromatography Pure fractions were evaporated 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 tert-butyl 4-(2-(2-chloroacetamido)ethyl)-4-hydroxypiperidine-1-carboxylate (example 89, step c) (0.3 g) in dry THF (18 mL) was added dropwise over 6 hours to a refluxing mixture of potassium tert-butoxide (1M in tert-butanol, 3 mL) and dry THF (60 mL). At the end of the addition the mixture was heated at reflux for a further 15 minutes and then cooled to room temperature. The mixture was partitioned between ethyl acetate and brine. The organic layer was dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. Trituration with diethylether afforded the subtitled compound. Yield 0.117 g. At the end of the addition the mixture was heated at reflux for a further 15 minutes The mixture was partitioned between ethyl acetate and brine The organic layer was dried over sodium sulphate filtered the solvent evaporated under reduced pressure

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Borane-methyl sulfide complex (2M in THF, 2.88 mL) was added to a solution of tert-butyl 9-oxo-7-oxa-3,10-diazaspiro[5.6]dodecane-3-carboxylate (example 89, step d) (0.41 g) in dry THF (40 mL) and the reaction mixture then heated at 70° C. for 30 minutes under nitrogen. The mixture was cooled to room temperature and quenched with methanol. The solvents were removed under reduced pressure and the residue dissolved in methanol (100 mL). N1,N2-dimethylethane-1,2-diamine (1.0 g) was added and the mixture heated at reflux under nitrogen for 16 h. Further N1,N2-dimethylethane-1,2-diamine (1.0 g) was added and refluxing continued for 16 h. The solvents were evaporated under reduced pressure and the residue azeotroped with toluene. The crude product was purified by flash silica chromatography using 6% methanol in dichloromethane with 1% triethylamine as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.176 g. The mixture was cooled to room temperature quenched with methanol The solvents were removed under reduced pressure the residue dissolved in methanol (100 mL) N1,N2-dimethylethane-1,2-diamine (1.0 g) was added the mixture heated at reflux under nitrogen for 16 h Further N1,N2-dimethylethane-1,2-diamine (1.0 g) was added refluxing The solvents were evaporated under reduced pressure the residue azeotroped with toluene The crude product was purified by flash silica chromatography Pure fractions were evaporated 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 tert-butyl 4-(2-(2-chloroacetamido)ethyl)-4-hydroxypiperidine-1-carboxylate (example 89, step c) (0.3 g) in dry THF (18 mL) was added dropwise over 6 hours to a refluxing mixture of potassium tert-butoxide (1M in tert-butanol, 3 mL) and dry THF (60 mL). At the end of the addition the mixture was heated at reflux for a further 15 minutes and then cooled to room temperature. The mixture was partitioned between ethyl acetate and brine. The organic layer was dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. Tritruration with diethylether afforded the subtitled compound. Yield 0.117 g. At the end of the addition the mixture was heated at reflux for a further 15 minutes The mixture was partitioned between ethyl acetate and brine The organic layer was dried over sodium sulphate filtered the solvent evaporated under reduced pressure