1,1'-Carbonyldiimidazole → 4-Amino-N-(1-azabicyclo[2.2.2]octan-3-yl)-5-chloro-2-hydroxybenzamide

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Reaction Steps

A solution of 4-amino-5-chloro-2-hydroxybenzoic acid (5.63 g, 30 mmole) in anhydrous tetrahydrofuran (30 ml) under nitrogen is treated with 1,1'-carbonyldiimidazole (5.03 g, 31 mmole), stirred at room temperature for one hour, and degassed by bubbling nitrogen over 20 minutes. A solution of 3-aminoquinuclidine(1) (from 36 mmole of the dihydrochloride) in anhydrous tetrahydrofuran (20 ml) is added, and the mixture is stirred at room temperature for 18 hours and at 50° C. for one hour. The resultant suspension is diluted with ether (50 ml) and filtered, and the solid is washed with ether. Successive trituration from acetonitrile and warm methanol provides 7.95 g (90%) of product as a pale tan solid, mp 300°-302° C. (dec.).

Provenance & Evidence