反应详情

温度

70 °C

To a solution of ethyl 1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl) -4-(3,4,5-trimethoxybenzoyl)piperazine-2-carboxylate (1.2 g) in methanol (15 ml) are added potassium carbonate (3.0 g) and water (8 ml) and the mixture is stirred at 70° C. for 30 minutes. To the reaction mixture is added water (50 ml). The mixture is washed with ethyl acetate. The aqueous layer is made acid with dilute hydrochloric acid, followed by extraction with ethyl acetate. The organic layer is washed with water, dried and concentrated under reduced pressure to give a crude product of 1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl) -4-(3,4,5-trimethoxybenzoyl)piperazine-2-carboxylic acid (1.1 g) as a colorless oily substance. To a mixture of this crude product (0.75 g), triethylamine (0.14 g) and N,N-dimethylformamide (4 ml) is added dropwise, while stirring under ice-cooling, diphenylphosphoryl azide (0.37 g). The reaction mixture is poured into ice-water, followed by extraction with benzene. The organic layer is washed with water and dried, followed by distilling off the solvent under reduced pressure until the whole volume becomes about 20 ml. The resultant solution is heated under reflux for 30 minutes. To the mixture is added methanol (5 ml), followed by heating under reflux for further one hour. The reaction mixture is concentrated under reduced pressure, and the concentrate is purified by means of a silica gel column chromatography (eluent hexane ethyl acetate-acetone=1:1:1) to give crystals, which are recrystallized from ethyl acetate to give 1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl) -2-methoxycarbonylamino-4-(3,4,5-trimethoxybenzoyl)piperazine as colorless crystals (0.6 g), m.p. 143-145° C.

1. washThe mixture is washed with ethyl acetate
2. extractionfollowed by extraction with ethyl acetate
3. washThe organic layer is washed with water
4. customdried
5. concentrationconcentrated under reduced pressure