5,7-difluoro-2,3-dihydroinden-1-one

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

実験手順: A 1000 ml 3-neck round bottom flask, fitted with an overhead stirrer, was charged with 5,7-difluoro-2,3-dihydro-1H-indene-1-one (10 g, 59.4 mmol) followed by dry dichloromethane (100 ml) and methanesulfonic acid (71.3 ml, 1.1 mol). The reaction was cooled to 0° C. (ice bath) and to this was added sodium azide (5.41 g; 83.2 mmol) in 4 equal portions over 20 minutes. The reaction was stirred at 0° C. for 2 hours and then a 20% aqueous solution of sodium hydroxide (175 ml) was added over 30 minutes with vigorous stirring. After complete addition the mixture was transferred to a separatory funnel and the methylene chloride phase was isolated. This was shaken with an equal volume of 50% diluted brine solution. The organic phase was collected and the aqueous phases were back extracted with dichloromethane (2×80 ml). The organic phases were combined, dried (magnesium sulfate), filtered and concentrated in vacuo. The crude residue was purified via HPLC on silica gel, eluting with 40% to 95% ethyl acetate/hexanes to provide the desired product as a white solid (8.364 g). (M+H)+=184 m/e. A 1000 ml 3-neck round bottom flask, fitted with an overhead stirrer After complete addition the mixture was transferred to a separatory funnel The organic phase was collected the aqueous phases were back extracted with dichloromethane (2×80 ml) dried (magnesium sulfate) filtered concentrated in vacuo The crude residue was purified via HPLC on silica gel eluting with 40% to 95% ethyl acetate/hexanes

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

実験手順: Selectfluor™ (1.16 g, 3.27 mmol) was added to a solution of 5,7-difluoro-1-indanone (CAS No. 84315-25-3, 500 mg, 2.97 mmol) in MeOH (20 mL) at room temperature. The mixture was refluxed for 2 hours and cooled to room temperature. Then the solvent was distilled off under reduced pressure. The residue was treated with DCM and the insoluble matter was filtered off. Then the solvent was distilled off under reduced pressure. The residue was dissolved in MeCN (10 mL) and 5 N HCl (5 mL). The solution was stirred at room temperature for 1 hour, and then concentrated in vacuo. The residue was partitioned between AcOEt and H2O. The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo to afford the title compound (547 mg, 2.94 mmol). 1H NMR (400 MHz, CDCl3) at room temperature The mixture was refluxed for 2 hours Then the solvent was distilled off under reduced pressure The residue was treated with DCM the insoluble matter was filtered off Then the solvent was distilled off under reduced pressure The residue was dissolved in MeCN (10 mL) concentrated in vacuo The residue was partitioned between AcOEt and H2O The organic layer was washed with brine dried over MgSO4 concentrated in vacuo

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

実験手順: A 1000 ml 3-neck round bottom flask, fitted with an overhead stirrer, was charged with 5,7-difluoro-2,3-dihydro-1H-indene-1-one (10 g, 59.4 mmol) followed by dry dichloromethane (100 ml) and methanesulfonic acid (71.3 ml, 1.1 mol). The reaction was cooled to 0° C. (ice bath) and to this was added sodium azide (5.41 g; 83.2 mmol) in 4 equal portions over 20 minutes. The reaction was stirred at 0° C. for 2 hours and then a 20% aqueous solution of sodium hydroxide (175 ml) was added over 30 minutes with vigorous stirring. After complete addition the mixture was transferred to a separatory funnel and the methylene chloride phase was isolated. This was shaken with an equal volume of 50% diluted brine solution. The organic phase was collected and the aqueous phases were back extracted with dichloromethane (2×80 ml). The organic phases were combined, dried (magnesium sulfate), filtered and concentrated in vacuo. The crude residue was purified via HPLC on silica gel, eluting with 40% to 95% ethyl acetate/hexanes to provide the desired product as a white solid (8.364 g). (M+H)+=184 m/e. A 1000 ml 3-neck round bottom flask, fitted with an overhead stirrer After complete addition the mixture was transferred to a separatory funnel The organic phase was collected the aqueous phases were back extracted with dichloromethane (2×80 ml) dried (magnesium sulfate) filtered concentrated in vacuo The crude residue was purified via HPLC on silica gel eluting with 40% to 95% ethyl acetate/hexanes

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

実験手順: A 1000 ml 3-neck round bottom flask, fitted with an overhead stirrer, was charged with 5,7-difluoro-2,3-dihydro-1H-indene-1-one (10 g, 59.4 mmol) followed by dry dichloromethane (100 ml) and methanesulfonic acid (71.3 ml, 1.1 mol). The reaction was cooled to 0° C. (ice bath) and to this was added sodium azide (5.41 g; 83.2 mmol) in 4 equal portions over 20 minutes. The reaction was stirred at 0° C. for 2 hours and then a 20% aqueous solution of sodium hydroxide (175 ml) was added over 30 minutes with vigorous stirring. After complete addition the mixture was transferred to a separatory funnel and the methylene chloride phase was isolated. This was shaken with an equal volume of 50% diluted brine solution. The organic phase was collected and the aqueous phases were back extracted with dichloromethane (2×80 ml). The organic phases were combined, dried (magnesium sulfate), filtered and concentrated in vacuo. The crude residue was purified via HPLC on silica gel, eluting with 40% to 95% ethyl acetate/hexanes to provide the desired product as a white solid (8.364 g). (M+H)+=184 m/e. A 1000 ml 3-neck round bottom flask, fitted with an overhead stirrer After complete addition the mixture was transferred to a separatory funnel The organic phase was collected the aqueous phases were back extracted with dichloromethane (2×80 ml) dried (magnesium sulfate) filtered concentrated in vacuo The crude residue was purified via HPLC on silica gel eluting with 40% to 95% ethyl acetate/hexanes