1,1'-Carbonyldiimidazole → 1H-Indole-3-carboxylic acid 1-azabicyclo[3.3.1]non-5-ylmethyl ester

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Reaction Steps

A solution of indole-3-carboxylic acid (1.62 g, 10 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (1.70 g, 10.5 mmol), stirred for one hour, and degassed with a stream of nitrogen for 10 minutes giving a suspension. Meanwhile, a cooled (-10° C.) solution of 1-azabicyclo[3.3.1]nonane-5-methanol (1.71 g, 11 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated (via syringe) with 2.5N n-butyllithium/hexane (10.7 mmol), stirred for 30 minutes, concentrated in vacuo, and taken up in anhydrous tetrahydrofuran (10 mL) under nitrogen. The 1,1'-carbonyldiimidazole adduct suspension was transferred into this solution, and the mixture was stirred overnight (18 hours) and concentrated in vacuo. The residue was partitioned between methylene chloride (100 mL) containing a little isopropanol and saturated sodium carbonate (50 mL), and the organic layer was separated. The aqueous solution was dried (Na2SO4), concentrated in vacuo, and filtered through alumina (eluted with 7% methanol/methylene chloride). The filtrated was concentrated in vacuo and the residue was triturated from cold ether and recrystallized from acetonitrile (2 crops) to afford 1.79 g (60%) of colorless crystals; m.p. 207°-209° C.

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