5-bromo-9-azatricyclo[8.1.1.02,7]dodeca-2(7),3,5-trien-8-one

反应条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Into a 5000-mL 3-necked round-bottom flask was placed 5-bromo-9-azatricyclo[8.1.1.0[2,7]]dodeca-2,4,6-trien-8-one (223 g, 884.55 mmol, 1.00 equiv), PhCH3 (3500 mL), PCl5 (560 g, 2.69 mol, 3.00 equiv), and DIPEA (275 g, 3.00 equiv). The resulting solution was stirred at 85° C. for 5 h and quenched by the addition of 300 g of DIPEA. The solids were filtered out and the filtrate was concentrated under vacuum to afford 260 g (crude) of 5-bromo-8-chloro-9-azatricyclo[8.1.1.0[2,7]]dodeca-2,4,6,8-tetraene as a black oil. Into a 5000-mL 3-necked round-bottom flask was placed quenched by the addition of 300 g of DIPEA The solids were filtered out the filtrate was concentrated under vacuum

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Into a 20-L 4-necked round-bottom flask was placed 6-Bromo-2,3-dihydro-1H-1,3-methano-naphthalen-4-one oxime (790 g, 3.13 mol, 1.00 equiv), 1,4-dioxane (7.5 L), followed by the addition of a solution of thionyl chloride (12000 g, 32.00 equiv) in 1,4-dioxane (7.5 L) dropwise with stirring at 25° C. The resulting solution was stirred at 65° C. for 6 h. This reaction was repeated for 2 more times. The resulting mixture was concentrated under vacuum, diluted with 10 L of DCM and then quenched by the addition of 8 L of water. The resulting solution was extracted with 2×10 L of dichloromethane and the organic layers were combined. The pH value of the solution was adjusted to 7 with sodium bicarbonate (sat.). The organic layer was dried over anhydrous sodium sulfated and concentrated under vacuum. The residue was diluted with 4 L of EA and stirred at reflux for 0.5 h. The solids were collected by filtration and washed with 2×500 mL, of EA. The filtrate was concentrated under vacuum. The residue was applied onto a silica gel column eluting with PE:EA (5:1-3:1). This solid was combined with the previous solids to afford 1749 g (74%) of 5-Bromo-9-aza-tricyclo[8.1.1.0[2,7]]dodeca-2,4,6-trien-8-one as an off-white solid. Into a 20-L 4-necked round-bottom flask was placed The resulting solution was stirred at 65° C. for 6 h The resulting mixture was concentrated under vacuum diluted with 10 L of DCM quenched by the addition of 8 L of water The resulting solution was extracted with 2×10 L of dichloromethane The organic layer was dried over anhydrous sodium concentrated under vacuum The residue was diluted with 4 L of EA stirred at reflux for 0.5 h The solids were collected by filtration washed with 2×500 mL, of EA The filtrate was concentrated under vacuum eluting with PE

反应条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Into a 5000-mL 3-necked round-bottom flask was placed 5-bromo-9-azatricyclo[8.1.1.0[2,7]]dodeca-2,4,6-trien-8-one (223 g, 884.55 mmol, 1.00 equiv), PhCH3 (3500 mL), PCl5 (560 g, 2.69 mol, 3.00 equiv), and DIPEA (275 g, 3.00 equiv). The resulting solution was stirred at 85° C. for 5 h and quenched by the addition of 300 g of DIPEA. The solids were filtered out and the filtrate was concentrated under vacuum to afford 260 g (crude) of 5-bromo-8-chloro-9-azatricyclo[8.1.1.0[2,7]]dodeca-2,4,6,8-tetraene as a black oil. Into a 5000-mL 3-necked round-bottom flask was placed quenched by the addition of 300 g of DIPEA The solids were filtered out the filtrate was concentrated under vacuum

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Into a 20-L 4-necked round-bottom flask was placed 6-Bromo-2,3-dihydro-1H-1,3-methano-naphthalen-4-one oxime (790 g, 3.13 mol, 1.00 equiv), 1,4-dioxane (7.5 L), followed by the addition of a solution of thionyl chloride (12000 g, 32.00 equiv) in 1,4-dioxane (7.5 L) dropwise with stirring at 25° C. The resulting solution was stirred at 65° C. for 6 h. This reaction was repeated for 2 more times. The resulting mixture was concentrated under vacuum, diluted with 10 L of DCM and then quenched by the addition of 8 L of water. The resulting solution was extracted with 2×10 L of dichloromethane and the organic layers were combined. The pH value of the solution was adjusted to 7 with sodium bicarbonate (sat.). The organic layer was dried over anhydrous sodium sulfated and concentrated under vacuum. The residue was diluted with 4 L of EA and stirred at reflux for 0.5 h. The solids were collected by filtration and washed with 2×500 mL, of EA. The filtrate was concentrated under vacuum. The residue was applied onto a silica gel column eluting with PE:EA (5:1-3:1). This solid was combined with the previous solids to afford 1749 g (74%) of 5-Bromo-9-aza-tricyclo[8.1.1.0[2,7]]dodeca-2,4,6-trien-8-one as an off-white solid. Into a 20-L 4-necked round-bottom flask was placed The resulting solution was stirred at 65° C. for 6 h The resulting mixture was concentrated under vacuum diluted with 10 L of DCM quenched by the addition of 8 L of water The resulting solution was extracted with 2×10 L of dichloromethane The organic layer was dried over anhydrous sodium concentrated under vacuum The residue was diluted with 4 L of EA stirred at reflux for 0.5 h The solids were collected by filtration washed with 2×500 mL, of EA The filtrate was concentrated under vacuum eluting with PE