3,4-dihydro-2H-1,4-benzoxazepin-5-one

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: The chroman-4-one (5.0 g, 33.8 mmol) was dissolved in sulfuric acid (10 mL) and the mixture was cooled at 0° C. Sodium azide (2.88 g, 44.3 mmol) was added portionwise followed by some sulfuric acid (5 mL). The reaction mixture was stirred at room temperature over night. The mixture was then pour into ice-water and basified to pH=7 with potassium hydroxide pellets. This aqueous layer was extracted with ether (twice). This aqueous layer was extracted with ether (twice)

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

実験手順: In 20 ml of dimethylformamide (DMF) was dissolved 100 mg of 2,3,4,5-tetrahydro-1,4-benzoxazepin-5-one, and the solution then ice-cooled. Then, to the resulting solution were added 0.251 ml (3 equivalents) of 1,5-dibromopentane and 29.4 mg (1.2 equivalent) of a 60% sodium hydride oil dispersion, and the mixture was stirred for one hour with ice-cooling. The reaction solution was poured into a citric acid aqueous solution and extracted with ethyl acetate, and the ethyl acetate phase was washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was then concentrated and the resulting residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (8:2)) to give 124 mg (yield: 65.0%) of the title compound. the solution then ice-cooled cooling extracted with ethyl acetate the ethyl acetate phase was washed with an aqueous saturated sodium chloride solution dried over anhydrous magnesium sulfate filtered The filtrate was then concentrated the resulting residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (8:2))

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

実験手順: To a solution of 1.5 g of 2,3,4,5-tetrahydro-1,4-benzoxazepin-5-one in 20 ml of tetrahydrofuran, was added 0.5 g of lithium aluminium hydride by portion, and the mixture was heated and refluxed for 2 hours. The reaction mixture was cooled to the room temperature. To the reaction mixture were added dropwise 1 ml of water and 0.8 ml of 10% aqueous solution of sodium hydroxide, and the mixture was stirred for 6 hours at room temperature. After the resultant solid mater was removed by filtration, the filtrate was concentrated under reduced pressure, and 20 ml of dichloromethane was added to the residue. The solution was dried over anhydrous sodium sulfate, then to the solution was added 0.94 ml of acetic anhydride, the mixture was stirred for 15 minutes at room temperature. The solvent was distilled off under reduced pressure, and the resulting oily residue was purified by means of column chromatography (developing solvent: dichloromethane-ethyl acetate=5:1 (V/V)) to give 1.8 g of 4-acetyl-2,3,4,5-tetrahydro-1,4-benzoxazepine as a colorless oily substance. The compound was used in the following steps without further purification. the mixture was heated refluxed for 2 hours After the resultant solid mater was removed by filtration the filtrate was concentrated under reduced pressure, and 20 ml of dichloromethane was added to the residue The solution was dried over anhydrous sodium sulfate to the solution was added 0.94 ml of acetic anhydride the mixture was stirred for 15 minutes at room temperature The solvent was distilled off under reduced pressure the resulting oily residue was purified by means of column chromatography (developing solvent: dichloromethane-ethyl acetate=5:1 (V/V))

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

実験手順: To a solution of 1.5 g of 2,3,4,5-tetrahydro-1,4-benzoxazepin-5-one in 20 ml of tetrahydrofuran, was added 0.5 g of lithium aluminium hydride by portion, and the mixture was heated and refluxed for 2 hours. The reaction mixture was cooled to the room temperature. To the reaction mixture were added dropwise 1 ml of water and 0.8 ml of 10% aqueous solution of sodium hydroxide, and the mixture was stirred for 6 hours at room temperature. After the resultant solid mater was removed by filtration, the filtrate was concentrated under reduced pressure, and 20 ml of dichloromethane was added to the residue. The solution was dried over anhydrous sodium sulfate, then to the solution was added 0.94 ml of acetic anhydride, the mixture was stirred for 15 minutes at room temperature. The solvent was distilled off under reduced pressure, and the resulting oily residue was purified by means of column chromatography (developing solvent: dichloromethane-ethyl acetate=5:1 (V/V)) to give 1.8 g of 4-acetyl-2,3,4,5-tetrahydro-1,4-benzoxazepine as a colorless oily substance. The compound was used in the following steps without further purification. the mixture was heated refluxed for 2 hours After the resultant solid mater was removed by filtration the filtrate was concentrated under reduced pressure, and 20 ml of dichloromethane was added to the residue The solution was dried over anhydrous sodium sulfate to the solution was added 0.94 ml of acetic anhydride the mixture was stirred for 15 minutes at room temperature The solvent was distilled off under reduced pressure the resulting oily residue was purified by means of column chromatography (developing solvent: dichloromethane-ethyl acetate=5:1 (V/V))

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: The chroman-4-one (5.0 g, 33.8 mmol) was dissolved in sulfuric acid (10 mL) and the mixture was cooled at 0 oC. Sodium azide (2.88 g, 44.3 mmol) was added portionwise followed by some sulfuric acid (5 mL). The reaction mixture was stirred at room temperature over night. The mixture was then pour into ice-water and basified to pH=7 with potassium hydroxide pellets. This aqueous layer was extracted with ether (twice). the mixture was cooled at 0 oC This aqueous layer was extracted with ether (twice)

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

実験手順: The chroman-4-one (5.0 g, 33.8 mmol) was dissolved in sulfuric acid (10 mL) and the mixture was cooled at 0° C. Sodium azide (2.88 g, 44.3 mmol) was added portionwise followed by some sulfuric acid (5 mL). The reaction mixture was stirred at room temperature over night. The mixture was then pour into ice-water and basified to pH=7 with potassium hydroxide pellets. This aqueous layer was extracted with ether (twice). This aqueous layer was extracted with ether (twice)

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

実験手順: In 20 ml of dimethylformamide (DMF) was dissolved 100 mg of 2,3,4,5-tetrahydro-1,4-benzoxazepin-5-one, and the solution then ice-cooled. Then, to the resulting solution were added 0.251 ml (3 equivalents) of 1,5-dibromopentane and 29.4 mg (1.2 equivalent) of a 60% sodium hydride oil dispersion, and the mixture was stirred for one hour with ice-cooling. The reaction solution was poured into a citric acid aqueous solution and extracted with ethyl acetate, and the ethyl acetate phase was washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was then concentrated and the resulting residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (8:2)) to give 124 mg (yield: 65.0%) of the title compound. the solution then ice-cooled cooling extracted with ethyl acetate the ethyl acetate phase was washed with an aqueous saturated sodium chloride solution dried over anhydrous magnesium sulfate filtered The filtrate was then concentrated the resulting residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (8:2))

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

実験手順: A mixture of 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one (200 mg, 0.69 mmol), 4-bromo-1-methylpyridin-2(1H)-one (156 mg, 0.83 mmol), cesium carbonate (674 mg, 2.07 mmol), 1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (49 mg, 0.069 mmol) was dissolved in a degassed mixture of DMF and water 3/1.5 (4.5 mL). The mixture was heated in microwave at 85° C. for 40 min. The mixture was poured into EtOAc and washed with water and brine. The organic layer was collected, dried over sodium sulfate and loaded onto silica gel. A flash column (5% MeOH in EtOAc) and reverse phase chromatography gave 7-ethyl-2-oxo-1,2-dihydropyridin-4-yl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one. washed with water and brine The organic layer was collected dried over sodium sulfate

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

実験手順: To 2,3,4,5-tetrahydro-1,4-benzoxazepin-5-one (30.34 g, 190 mmol) in conc. sulfuric acid (600 ml) at 0° C. was added potassium nitrate (20.82 g, 206 mmol) portionwise. The mixture was stirred for 20 minutes at 0° C. and then for 4 h at room temperature. The mixture was poured onto ice (21) and the solids were collected by filtration. The solids were taken up in hot ethyl acetate and then cooled to yield the title compound (8.79 g, 22%), MS m/z 209 [M+H]+. for 4 h at room temperature the solids were collected by filtration cooled

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 4-chromanone (50 g, 340 mmol) in acetic acid (670 ml) was added sodium azide (66.31 g, 1.02 mol) and conc. sulfuric acid (100 ml) dropwise at 0° C. The mixture was heated to 50° C. for 4 h and then cooled to room temperature. The mixture was poured onto ice (1 l) and basified with conc. ammonium hydroxide. The mixture was stirred for 24 h and the solids were collected by filtration (30.43 g, 55%), MSm/z 164 [M+H]+. cooled to room temperature The mixture was poured onto ice (1 l) the solids were collected by filtration (30.43 g, 55%), MSm/z 164 [M+H]+