阿哌沙班杂质67

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

实验步骤: Toluene (100 ml), ethanol (10.12 g, 219.65 mmol) and 5-chlorovaleric acid (25 g, 183.04 mmol) were added into a 200-ml flask in this order at room temperature and then p-toluenesulfonic acid monohydrate (5.22 g, 27.46 mmol) was charged thereto. The solution was gently heated and subjected to reflux dehydration for 3 to 5 hours. After reflux dehydration, the solution was cooled to around room temperature, added with triethylamine (4.63 g, 45.76 mmol) at room temperature, stirred and then added with silica gel. After stirring for a while, the silica gel was filtered off. After the solvent of the filtrate was removed in vacuum distillation, ethyl 5-chlorovalerate (21.54 g, 72%) was isolated in distillation. The solution was gently heated to reflux dehydration for 3 to 5 hours After reflux dehydration the solution was cooled to around room temperature added with silica gel After stirring for a while the silica gel was filtered off After the solvent of the filtrate was removed in vacuum distillation

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

实验步骤: Toluene (100 ml), ethanol (10.12 g, 219.65 mmol) and 5-chlorovaleric acid (25 g, 183.04 mmol) were added into a 200-ml flask in this order at room temperature and then p-toluenesulfonic acid monohydrate (5.22 g, 27.46 mmol) was charged thereto. The solution was gently heated and subjected to reflux dehydration for 3 to 5 hours. After reflux dehydration, the solution was cooled to around room temperature, added with triethylamine (4.63 g, 45.76 mmol) at room temperature, stirred and then added with silica gel. After stirring for a while, the silica gel was filtered off. After the solvent of the filtrate was removed in vacuum distillation, ethyl 5-chlorovalerate (21.54 g, 72%) was isolated in distillation. The solution was gently heated to reflux dehydration for 3 to 5 hours After reflux dehydration the solution was cooled to around room temperature added with silica gel After stirring for a while the silica gel was filtered off After the solvent of the filtrate was removed in vacuum distillation