Carbon Dioxide → N-Methyl-1H-indole-5-acetamide

Participants

Reaction Steps

4-Nitrobenzeneacetic acid (16.6 g, 0.0916 mol) was dissolved in THF (200 mL) and carbonyldiimidazole (CDI, 15.6 g, 0.0963 mol) was added. Carbon dioxide evolution rapidly ensued and the reaction mixture was stirred at RT for 30 min. Gaseous methylamine was then bubbled through the mixture until it was distinctly basic to litmus paper. The THF was removed in vacuo and water (70 mL) was added. The solid material was collected by filtration and placed in a Parr bottle were palladium on carbon (10%, 3 g). A solution of EtOH (200 mL) and 1N HCl (50 mL) was added and the mixture was hydrogenated at 60 psi for 4 h. The reaction was filtered, concentrated in vacuo and the residue made basic with saturated aqueous Na2CO3. The aqueous mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give the product (6) (10.0 g, 66.6%) which was pure by NMR analysis.

Provenance & Evidence