反应详情

A solution of 5-chloro-2-methoxy-4-(methylamino)-benzoic acid (1.95 g, 9.0 mmoles) in anhydrous tetrahydrofuran (10 ml) was treated with 1,1'-carbonyldiimidazole (1.49 g, 9.2 mmoles), stirred at room temperature for 90 minutes, then added to a cooled (0° C.) solution of 2-(1-piperidylmethyl)-1-azabicyclo[2.2.2]octan-3-amine (2.12 g, 9.5 mmoles) in anhydrous tetrahydrofuran (10 ml) under nitrogen. After 18 hours at room temperature the solution was concentrated in vacuo and partitioned between methylene chloride (100 ml) and 1.0N sodium hydroxide (40 ml). The organic solution was separated and washed with 1.0N sodium hydroxide (40 ml), saturated aqueous sodium bicarbonate (40 ml), and brine (40 ml), dried (Na2SO4), and concentrated in vacuo. Filtration through alumina (eluted with 15% methanol/ethyl acetate) provided 3.24 g (86%) of a colorless foam.

1. additionadded to
2. concentrationAfter 18 hours at room temperature the solution was concentrated in vacuo
3. custompartitioned between methylene chloride (100 ml) and 1.0N sodium hydroxide (40 ml)
4. customThe organic solution was separated
5. washwashed with 1.0N sodium hydroxide (40 ml), saturated aqueous sodium bicarbonate (40 ml), and brine (40 ml)
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated in vacuo
8. filtrationFiltration through alumina (eluted with 15% methanol/ethyl acetate)