methyl 5-oxo-6,7,8,9-tetrahydrobenzo[7]annulene-6-carboxylate

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of benzosuberone (8 g, 50 mmol) and neat dimethyl carbonate (45 mL) at ambient temperature under N2 was treated with NaH (60% in mineral oil, 4 g, 100 mmol) in 0.1 mL of dry MeOH, heated at 80° C. for 3 hours, cooled to ambient temperature, treated with 2 N HCl (55 mL) and extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4) and concentrated to provide the title compound as an oil, as a 3:1 mixture of enol and keto forms of product by NMR spectroscopy. The NMR of the main enol form was: 1H NMR (CDCl3) δ 2.03-2.16 (m, 4H), 2.64 (m, 2H), 3.82 (s, 3H), 7.23 (m, 1H), 7.33 (m, 2H), 7.62 (m, 1H), 12.6 (bs, 1H). MS (M+H)+ m/z 219. cooled to ambient temperature extracted with ethyl acetate The organic layer was washed with brine dried (MgSO4) concentrated

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

実験手順: A solution of the product from Example 4A (4.2 g, est. 18 mmol), guanidine chloride (7.1 g, 72.8 mmol), and K2CO3 (10.8 g, 78 mmol) in DMF (30 mL) was heated to 125° C. for 3 hours. The mixture was cooled and the solids were removed by filtration. The solids were washed with EtOAc. The combined filtrates were concentrated under reduced pressure and the residue was passed through silica gel pad eluting with EtOAc:hexanes (8:2) and then with MeOH:EtOAc:CH2Cl2 (10:45:45) to provide the title compound as a white solid (2.8 g). The mixture was cooled the solids were removed by filtration The solids were washed with EtOAc The combined filtrates were concentrated under reduced pressure eluting with EtOAc:hexanes (8:2)

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

実験手順: A solution of the product from Example 4A (4.2 g, est. 18 mmol), guanidine chloride (7.1 g, 72.8 mmol), and K2CO3 (10.8 g, 78 mmol) in DMF (30 mL) was heated to 125° C. for 3 hours. The mixture was cooled and the solids were removed by filtration. The solids were washed with EtOAc. The combined filtrates were concentrated under reduced pressure and the residue was passed through silica gel pad eluting with EtOAc:hexanes (8:2) and then with MeOH:EtOAc:CH2Cl2 (10:45:45) to provide the title compound as a white solid (2.8 g). The mixture was cooled the solids were removed by filtration The solids were washed with EtOAc The combined filtrates were concentrated under reduced pressure eluting with EtOAc:hexanes (8:2)

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of dimethyl carbonate (20 mL) was treated with NaH (3 g, 60% dispersed in oil, 75 mmol) and heated to 85° C. To the mixture was dropwise added a solution of bezosuberone (3 g, 18.75 mmol) in dimethyl carbonate (10 mL). The resulting mixture was refluxed for 3 hours, cooled to 0° C., quenched with HCl (1N) (100 mL) and extracted with ether. The organic layer was washed with NaHCO3 and brine, dried (MgSO4) and concentrated to provide the title compound as a brownish oil. The resulting mixture was refluxed for 3 hours cooled to 0° C. quenched with HCl (1N) (100 mL) extracted with ether The organic layer was washed with NaHCO3 and brine dried (MgSO4) concentrated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of benzosuberone (8 g, 50 mmol) and neat dimethyl carbonate (45 mL) at ambient temperature under nitrogen was treated with sodium hydride (60% in mineral oil, 4 g, 100 mmol) in 0.1 mL of dry methanol, heated at 80° C. for 3 hours, cooled to ambient temperature, treated with 2 N hydrochloric acid (55 mL) and extracted with ethyl acetate. The organic layer was washed with brine, dried (magnesium sulfate) and concentrated to provide the title compound as an oil, as a 3:1 mixture of enol and keto forms of product determined by NMR spectroscopy. The NMR of the main enol form was: 1H NMR (CDCl3) δ 2.03-2.16 (m, 4H), 2.64 (m, 2H), 3.82 (s, 3H), 7.23 (m, 1H), 7.33 (m, 2H), 7.62 (m, 1H), 12.6 (br s, 1H); MS (ESI+) m/z 219 (M+H)−. cooled to ambient temperature extracted with ethyl acetate The organic layer was washed with brine dried (magnesium sulfate) concentrated

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

実験手順: To a solution of 6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-5-one (24.99 g, 156.0 mmol) and dimethyl carbonate (42.2 g, 468 mmol) in tetrahydrofuran (150 ml) was added a suspension (12.5 g, 312 mmol) of 60% sodium hydride in liquid paraffin at room temperature and the mixture was heated under reflux for 1 hr. The reaction solution was poured into water, acidified with 1N hydrochloric acid and extracted twice with ethyl acetate. The collected organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=15/1) to give methyl 5-oxo-6,7,8,9-tetrahydro-5H-benzo[a]cycloheptene-6-carboxylate as a yellow liquid. the mixture was heated under reflux for 1 hr extracted twice with ethyl acetate The collected organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=15/1)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of benzosuberone (8 g, 50 mmol) and neat dimethyl carbonate (45 mL) at ambient temperature under N2 was treated with NaH (60% in mineral oil, 4 g, 100 mmol) in 0.1 mL of dry MeOH, heated at 80° C. for 3 hours, cooled to ambient temperature, treated with 2 N HCl (55 mL) and extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4) and concentrated to provide the title compound as an oil, as a 3:1 mixture of enol and keto forms of product by NMR spectroscopy. The NMR of the main enol form was: 1H NMR (CDCl3) δ 2.03-2.16 (m, 4H), 2.64 (m, 2H), 3.82 (s, 3H), 7.23 (m, 1H), 7.33 (m, 2H), 7.62 (m, 1H), 12.6 (bs, 1H). MS (M+H)+ m/z 219. cooled to ambient temperature extracted with ethyl acetate The organic layer was washed with brine dried (MgSO4) concentrated

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

実験手順: A solution of the product from Example 4A (4.2 g, est. 18 mmol), guanidine chloride (7.1 g, 72.8 mmol), and K2CO3 (10.8 g, 78 mmol) in DMF (30 mL) was heated to 125° C. for 3 hours. The mixture was cooled and the solids were removed by filtration. The solids were washed with EtOAc. The combined filtrates were concentrated under reduced pressure and the residue was passed through silica gel pad eluting with EtOAc:hexanes (8:2) and then with MeOH:EtOAc:CH2Cl2 (10:45:45) to provide the title compound as a white solid (2.8 g). The mixture was cooled the solids were removed by filtration The solids were washed with EtOAc The combined filtrates were concentrated under reduced pressure eluting with EtOAc:hexanes (8:2)

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of dimethyl carbonate (20 mL) was treated with NaH (3 g, 60% dispersed in oil, 75 mmol) and heated to 85° C. To the mixture was dropwise added a solution of bezosuberone (3 g, 18.75 mmol) in dimethyl carbonate (10 mL). The resulting mixture was refluxed for 3 hours, cooled to 0° C., quenched with HCl (1N) (100 mL) and extracted with ether. The organic layer was washed with NaHCO3 and brine, dried (MgSO4) and concentrated to provide the title compound as a brownish oil. The resulting mixture was refluxed for 3 hours cooled to 0° C. quenched with HCl (1N) (100 mL) extracted with ether The organic layer was washed with NaHCO3 and brine dried (MgSO4) concentrated