3-(methylamino)-2,3,4,5-tetrahydro-1-benzoxepin-5-ol

反応条件: temp:0.00; pressure:0.00; stir:

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: 1.93 g of 3-methylamino-2,3,4,5-tetrahydro-1-benzoxepin-5-ol were added to 25 ml of ethylene glycol dimethyl ether and reacted with 1.5 g aluminum trichloride while cooling with ice. Subsequently, the reaction mixture was heated for 18 hours at boiling temperature. Thereafter, the solvent was evaporated; the residue was dissolved in water, and the solution was reacted with diluted sodium hydroxide solution and extracted with methylene chloride. The methylene chloride extract was evaporated, and the 3-methylamino-2,3-dihydro-1-benzoxepine which remained as a residue was converted to its hydrochloride as described in Example 1, and this was recrystallized from a methanol/ether mixture. 1.9 g of 3-methylamino-2,3-dihydro-1-benzoxepine hydrochloride were obtained. Melting point: 168°-170 degrees C. while cooling with ice Subsequently, the reaction mixture was heated for 18 hours Thereafter, the solvent was evaporated the residue was dissolved in water the solution was reacted with diluted sodium hydroxide solution extracted with methylene chloride The methylene chloride extract was evaporated this was recrystallized from a methanol/ether mixture

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

実験手順: 1.93 g of 3-methylamino-2,3,4,5-tetrahydro-1-benzoxepin-5-ol were added to 25 ml of ethylene glycol dimethyl ether and reacted with 1.5 g aluminum trichloride while cooling with ice. Subsequently, the reaction mixture was heated for 18 hours at boiling temperature. Thereafter, the solvent was evaporated; the residue was dissolved in water, and the solution was reacted with diluted sodium hydroxide solution and extracted with methylene chloride. The methylene chloride extract was evaporated, and the 3-methylamino-2,3-dihydro-1-benzoxepine which remained as a residue was converted to its hydrochloride as described in Example 1, and this was recrystallized from a methanol/ether mixture. 1.9 g of 3-methylamino-2,3-dihydro-1-benzoxepine hydrochloride were obtained. Melting point: 168°-170 degrees C. while cooling with ice Subsequently, the reaction mixture was heated for 18 hours Thereafter, the solvent was evaporated the residue was dissolved in water the solution was reacted with diluted sodium hydroxide solution extracted with methylene chloride The methylene chloride extract was evaporated this was recrystallized from a methanol/ether mixture

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: To a boiling solution of 80 g (0.5 mole) rac.-3-methylamino-3,4-dihydro-1-benzoxepin-5-(2H)-one in a mixture of 550 ml toluene and 300 ml hexane, 550 ml of a 1 molar solution of lithium-tri-sec.-butylborohydride in tetrahydrofuran are added in drops, so that the solution is maintained boiling. Following the completion of the addition, the mixture is heated to boiling for another hour. After cooling, the mixture is acidified by the drop-wise addition of methanolic hydrochloric acid. The methanol phase is then separated and the toluene/hexane mixture is again extracted with hydrochloric acid in methanol. The extracts are evaporated, taken up with dichloromethane and a solution (10%) of sodium carbonate, the organic phase washed with saturated sodium chloride, dried over sodium sulfate and evaporated to dryness. 67.6 g (70% of the theoretical yield) of rac.-2,3,4,5-tetrahydro-3-methylamino-1-benzoxepin-5-ol are obtained in the form of an oily residue, wherein rac.-cis-2,3,4,5-tetrahydro-3-methylamino-1-benzoxepin-5-ol predominates with 82 parts for 18 parts of rac.-trans-2,3,4,5 -tetrahydro-3-methylamino-1-benzoxepin-5-ol. The compounds may be separated and identified as described hereinabove. are added in drops, so that the solution is maintained the completion of the addition the mixture is heated to boiling for another hour After cooling The methanol phase is then separated the toluene/hexane mixture is again extracted with hydrochloric acid in methanol The extracts are evaporated a solution (10%) of sodium carbonate, the organic phase washed with saturated sodium chloride dried over sodium sulfate evaporated to dryness

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

実験手順: 18.8 g (0.1 mole) 3-methylamino-1-benzoxepin-5(2H)-one is stirred with 40 g Raney Nickel in 400 ml ethanol for five hours at an hydrogen pressure of 55 bar. Subsequently, the catalyst is filtered out, the solvent is distilled off and one obtains 7.7 g (40% of the theoretical yield) racemic-2,3,4,5-tetrahydro-3-methylamino-1-benzoxepin-5-ol as an oil. The compound can be further separated as described earlier and further identified. Subsequently, the catalyst is filtered out the solvent is distilled off one obtains 7.7 g (40% of the

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

実験手順: Sodium borohydride is added in small portions to a solution of 18.8 g (0.1 mole) 3-methylamino-1-benzoxepin-5-(2H)-one in a mixture of 125 ml dioxane and 125 ml acetic acid cooled in an ice bath. The reaction solution is maintained in a cooled state during the addition of the sodium borohydride (0.4 mole) up to the end of the reaction. The reaction solution is then poured into ice water, made alkaline with sodium carbonate and extracted with dichloromethane. The organic solution is washed with saturated salt solution and dried over sodium sulfate. After removal of the solvent, 16.4 g (85% of the theoretical yield) of racemic-2,3,4,5-tetrahydro-3-methylamino-1-benzoxepin-5-ol is recovered in the form of an oil. cooled in an ice bath extracted with dichloromethane The organic solution is washed with saturated salt solution dried over sodium sulfate After removal of the solvent, 16.4 g (85% of the

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

実験手順: 1.93 g of 3-methylamino-2,3,4,5-tetrahydro-1-benzoxepin-5-ol were added to 25 ml of ethylene glycol dimethyl ether and reacted with 1.5 g aluminum trichloride while cooling with ice. Subsequently, the reaction mixture was heated for 18 hours at boiling temperature. Thereafter, the solvent was evaporated; the residue was dissolved in water, and the solution was reacted with diluted sodium hydroxide solution and extracted with methylene chloride. The methylene chloride extract was evaporated, and the 3-methylamino-2,3-dihydro-1-benzoxepine which remained as a residue was converted to its hydrochloride as described in Example 1, and this was recrystallized from a methanol/ether mixture. 1.9 g of 3-methylamino-2,3-dihydro-1-benzoxepine hydrochloride were obtained. Melting point: 168°-170 degrees C. while cooling with ice Subsequently, the reaction mixture was heated for 18 hours Thereafter, the solvent was evaporated the residue was dissolved in water the solution was reacted with diluted sodium hydroxide solution extracted with methylene chloride The methylene chloride extract was evaporated this was recrystallized from a methanol/ether mixture