tert-butyl 3-oxocyclobutane-1-carboxylate

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 2000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 1-bromo-2-fluoro-4-iodobenzene (58 g, 192.76 mmol, 1.00 equiv) in tetrahydrofuran (600 mL), followed by the addition of i-PrMgCl (96.3 mL, 1.00 equiv) dropwise with stirring at 0° C. over 30 min. The mixture was stirred at 0° C. for 3 h. To this was added tert-butyl 3-oxocyclobutane-1-carboxylate (32.7 g, 192.12 mmol, 1.00 equiv) dropwise with stirring at −78° C. over 10 min. The mixture was stirred at −78 degree C. for 1 h and overnight at room temperature. The reaction was then quenched by the addition of 200 mL of saturated aqueous NH4Cl at 0° C. and extracted with 3×500 mL of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum to afford 62 g (crude) of tert-butyl 3-(4-bromo-3-fluorophenyl)-3-hydroxycyclobutane-1-carboxylate as a yellow oil. Into a 2000-mL 4-necked round-bottom flask purged maintained with an inert atmosphere of nitrogen The mixture was stirred at 0° C. for 3 h with stirring at −78° C. over 10 min The mixture was stirred at −78 degree C for 1 h overnight at room temperature The reaction was then quenched by the addition of 200 mL of saturated aqueous NH4Cl at 0° C. extracted with 3×500 mL of ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 2000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 1-bromo-2-fluoro-4-iodobenzene (58 g, 192.76 mmol, 1.00 equiv) in tetrahydrofuran (600 mL), followed by the addition of i-PrMgCl (96.3 mL, 1.00 equiv) dropwise with stirring at 0° C. over 30 min. The mixture was stirred at 0° C. for 3 h. To this was added tert-butyl 3-oxocyclobutane-1-carboxylate (32.7 g, 192.12 mmol, 1.00 equiv) dropwise with stirring at −78° C. over 10 min. The mixture was stirred at −78 degree C. for 1 h and overnight at room temperature. The reaction was then quenched by the addition of 200 mL of saturated aqueous NH4Cl at 0° C. and extracted with 3×500 mL of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum to afford 62 g (crude) of tert-butyl 3-(4-bromo-3-fluorophenyl)-3-hydroxycyclobutane-1-carboxylate as a yellow oil. Into a 2000-mL 4-necked round-bottom flask purged maintained with an inert atmosphere of nitrogen The mixture was stirred at 0° C. for 3 h with stirring at −78° C. over 10 min The mixture was stirred at −78 degree C for 1 h overnight at room temperature The reaction was then quenched by the addition of 200 mL of saturated aqueous NH4Cl at 0° C. extracted with 3×500 mL of ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum

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

実験手順: Into a 2000-mL 4-necked round-bottom flask was placed a solution of 3-oxocyclobutane-1-carboxylic acid (114 g, 999.13 mmol, 1.00 equiv) in dichloromethane (400 mL), 2-methylpropan-2-ol (102 g, 1.38 mol, 1.37 equiv), N,N-dimethylpyridin-4-amine (67.2 g, 550.06 mmol, 0.55 equiv), followed by the addition of a solution of N—(N-cyclohexylcarboximidoyl)cyclohexanamine (226.6 g, 1.10 mol, 1.10 equiv) in dichloromethane (300 mL) dropwise with stirring at room temperature over 25 min. The resulting solution was stifled overnight at room temperature. The solids were filtered out and the filtrate was washed with 2×500 mL of HCl (1 M) and 1×500 mL of saturated aqueous NaHCO3, and concentrated under vacuum. The residue was diluted with 500 mL of hexane. The mixture was decolorized by 50 g of active carbon and stirring for 3 minutes. The solids were filtered out and the filtrate was concentrated under vacuum to afford 102 g (60%) of tert-butyl 3-oxocyclobutane-1-carboxylate as a light yellow liquid. Into a 2000-mL 4-necked round-bottom flask was placed The resulting solution was stifled overnight at room temperature The solids were filtered out the filtrate was washed with 2×500 mL of HCl (1 M) and 1×500 mL of saturated aqueous NaHCO3 concentrated under vacuum The residue was diluted with 500 mL of hexane stirring for 3 minutes The solids were filtered out the filtrate was concentrated under vacuum

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

実験手順: Into a 2000-mL 4-necked round-bottom flask was placed a solution of 3-oxocyclobutane-1-carboxylic acid (114 g, 999.13 mmol, 1.00 equiv) in dichloromethane (400 mL), 2-methylpropan-2-ol (102 g, 1.38 mol, 1.37 equiv), N,N-dimethylpyridin-4-amine (67.2 g, 550.06 mmol, 0.55 equiv), followed by the addition of a solution of N—(N-cyclohexylcarboximidoyl)cyclohexanamine (226.6 g, 1.10 mol, 1.10 equiv) in dichloromethane (300 mL) dropwise with stirring at room temperature over 25 min. The resulting solution was stifled overnight at room temperature. The solids were filtered out and the filtrate was washed with 2×500 mL of HCl (1 M) and 1×500 mL of saturated aqueous NaHCO3, and concentrated under vacuum. The residue was diluted with 500 mL of hexane. The mixture was decolorized by 50 g of active carbon and stirring for 3 minutes. The solids were filtered out and the filtrate was concentrated under vacuum to afford 102 g (60%) of tert-butyl 3-oxocyclobutane-1-carboxylate as a light yellow liquid. Into a 2000-mL 4-necked round-bottom flask was placed The resulting solution was stifled overnight at room temperature The solids were filtered out the filtrate was washed with 2×500 mL of HCl (1 M) and 1×500 mL of saturated aqueous NaHCO3 concentrated under vacuum The residue was diluted with 500 mL of hexane stirring for 3 minutes The solids were filtered out the filtrate was concentrated under vacuum

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 2000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of 1-bromo-2-fluoro-4-iodobenzene (58 g, 192.76 mmol, 1.00 equiv) in tetrahydrofuran (600 mL), followed by the addition of i-PrMgCl (96.3 mL, 1.00 equiv) dropwise with stirring at 0° C. over 30 min. The mixture was stirred at 0° C. for 3 h. To this was added tert-butyl 3-oxocyclobutane-1-carboxylate (32.7 g, 192.12 mmol, 1.00 equiv) dropwise with stirring at −78° C. over 10 min. The mixture was stirred at −78 degree C. for 1 h and overnight at room temperature. The reaction was then quenched by the addition of 200 mL of saturated aqueous NH4Cl at 0° C. and extracted with 3×500 mL of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under vacuum to afford 62 g (crude) of tert-butyl 3-(4-bromo-3-fluorophenyl)-3-hydroxycyclobutane-1-carboxylate as a yellow oil. Into a 2000-mL 4-necked round-bottom flask purged maintained with an inert atmosphere of nitrogen The mixture was stirred at 0° C. for 3 h with stirring at −78° C. over 10 min The mixture was stirred at −78 degree C for 1 h overnight at room temperature The reaction was then quenched by the addition of 200 mL of saturated aqueous NH4Cl at 0° C. extracted with 3×500 mL of ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum

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

実験手順: Into a 2000-mL 4-necked round-bottom flask was placed a solution of 3-oxocyclobutane-1-carboxylic acid (114 g, 999.13 mmol, 1.00 equiv) in dichloromethane (400 mL), 2-methylpropan-2-ol (102 g, 1.38 mol, 1.37 equiv), N,N-dimethylpyridin-4-amine (67.2 g, 550.06 mmol, 0.55 equiv), followed by the addition of a solution of N—(N-cyclohexylcarboximidoyl)cyclohexanamine (226.6 g, 1.10 mol, 1.10 equiv) in dichloromethane (300 mL) dropwise with stirring at room temperature over 25 min. The resulting solution was stifled overnight at room temperature. The solids were filtered out and the filtrate was washed with 2×500 mL of HCl (1 M) and 1×500 mL of saturated aqueous NaHCO3, and concentrated under vacuum. The residue was diluted with 500 mL of hexane. The mixture was decolorized by 50 g of active carbon and stirring for 3 minutes. The solids were filtered out and the filtrate was concentrated under vacuum to afford 102 g (60%) of tert-butyl 3-oxocyclobutane-1-carboxylate as a light yellow liquid. Into a 2000-mL 4-necked round-bottom flask was placed The resulting solution was stifled overnight at room temperature The solids were filtered out the filtrate was washed with 2×500 mL of HCl (1 M) and 1×500 mL of saturated aqueous NaHCO3 concentrated under vacuum The residue was diluted with 500 mL of hexane stirring for 3 minutes The solids were filtered out the filtrate was concentrated under vacuum