反应详情

A solution of 5-chloro-2-methoxy-4-(methylamino)benzoic acid (3.35 g, 15.5 mmoles) in anhydrous tetrahydrofuran (20 ml) under nitrogen was treated with 1,1'-carbonyldiimidazole (2.56 g, 15.8 mmoles), and stirred for one hour at room temperature. Nitrogen was bubbled through the solution for 20 minutes, and a solution of 2-(di-n-propylaminomethyl)-1-azabicyclo[2.2.2]-octan-3-amine (3.95 g, 15.8 mmoles) in tetrahydrofuran (10 ml) was added dropwise. The mixture was maintained at room temperature for 18 hours, and at 50° C. for 1 hour, then concentrated in vacuo. The residue was partitioned between methylene chloride and 1.0N aqueous sodium carbonate, and the organic layer was separated. The aqueous solution was extracted with methylene chloride, and the combined organic solution was dried (Na2SO4) and concentrated in vacuo. The residue was filtered through alumina (eluted with 3% methanol/methylene chloride) to provide 5.38 g (79%) of a colorless foam.

1. customNitrogen was bubbled through the solution for 20 minutes
2. temperatureThe mixture was maintained at room temperature for 18 hours
3. waitat 50° C. for 1 hour
4. concentrationconcentrated in vacuo
5. customThe residue was partitioned between methylene chloride and 1.0N aqueous sodium carbonate
6. customthe organic layer was separated
7. extractionThe aqueous solution was extracted with methylene chloride
8. dry with materialthe combined organic solution was dried (Na2SO4)
9. concentrationconcentrated in vacuo
10. filtrationThe residue was filtered through alumina (eluted with 3% methanol/methylene chloride)