反应详情

温度

0 °C

A solution of 4-amino-5-chloro-2-(2-methoxyethoxy)benzoic acid (2.09 g, 8.5 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (1.46 g, 9.0 mmol), stirred for one hour, degassed under a stream of nitrogen over 10 minutes, and cooled (0° C.). A solution of 1-azabicyclo[3.3.1]nonane-5-methanamine (1.36 g, 8.8 mmol) in tetrahydrofuran (5 mL) was added dropwise, and stirring was continued at room temperature for 18 hours. The solution was concentrated in vacuo and the residue was taken up in methylene chloride (100 mL) and washed with saturated sodium carbonate (50 mL). The organic solution was dried (Na2SO4), concentrated in vacuo, and passed through a short column of alumina (eluted with 5% methanol/methylene chloride). The filtrate was concentrated in vacuo and, at this point, appeared to be contaminated with some highly insoluble impurity. The residue was taken up in tetrahydrofuran and filtered, and the filtrate was concentrated in vacuo, triturated from cold ether, and recrystallized from acetonitrile (2 crops) to afford 1.59 g (49%) of colorless crystals; mp 154.0°-155.5° C.

1. customdegassed under a stream of nitrogen over 10 minutes
2. stirringstirring
3. waitwas continued at room temperature for 18 hours
4. concentrationThe solution was concentrated in vacuo
5. washwashed with saturated sodium carbonate (50 mL)
6. dry with materialThe organic solution was dried (Na2SO4)
7. concentrationconcentrated in vacuo
8. concentrationThe filtrate was concentrated in vacuo and, at this point
9. filtrationfiltered
10. concentrationthe filtrate was concentrated in vacuo
11. customtriturated from cold ether
12. customrecrystallized from acetonitrile (2 crops)