1,1'-Carbonyldiimidazole → HCID 19883426, compound

Participants

Reaction Steps

A suspension of indole-3-carboxylic acid (1.94 g, 0.012 mole) in anhydrous 2:1 dimethylformamide/tetrahydrofuran (15 ml) under nitrogen was treated with 1,1'-carbonyldiimidazole (2.27 g, 0.014 mole), stirred for two hours, and degassed over 15 minutes with a stream of nitrogen. A solution containing 3-aminomethyl-1-azabicyclo[2.2.2]octan-3-ol in tetrahydrofuran (10 ml) was added and the mixture stirred for 18 hours at 25° C. and for four hours at 50° C., then concentrated in vacuo. The residue was partitioned between saturated sodium carbonate (75 ml) and toluene (150 ml) containing some 2-propanol, and the organic layer was separated. The aqueous solution was extracted with toluene (75 ml) containing some 2-propanol, and the combined organic solution was dried (sodium sulfate), and concentrated in vacuo. The gummy residue was washed with water, redissolved in toluene containing some 2-propanol, dried (sodium sulfate), concentrated in vacuo, and taken up in methanol (20 ml). A warm solution of fumaric acid (2.0 g, 0.0172 mole) in methanol (30 ml) was added, and after 15 minutes the solution was concentrated in vacuo to a gummy oil. This was triturated successively from ether, acetonitrile, and ethyl acetate to afford (after drying) 3.36 g (52%) of the title compound as a colorless solid.

Provenance & Evidence