Dimethylformamide → (S)-3-[(1-azabicyclo[2.2.2]oct-3-yl)aminocarbonyl]-1,2-dimethylindole

Participants

Reaction Steps

1,2-dimethylindole-3-carboxylic acid (1.05 g, 5.5 mmol) was dissolved with oxalyl chloride (0.55 ml, 6 mmol) and dimethylformamide (0.1 ml) in dichloromethane (30 ml) and stirred at room temperature for one hour. The mixture was then concentrated under reduced pressure, and the residue was dissolved in dichloromethane (20 ml). The resulting mixture was added dropwise at 0° C. to a solution of (S)-3-amino-1-azabicyclo[2.2.2]octane (0.7 g, 5.5 mmol) in dichloromethane (10 ml). The solution was stirred at room temperature for 30 minutes, after which the solvent was removed under vacuum. The residue was dissolved in water and washed with ethyl acetate. The aqueous layer was made basic with 10N aqueous sodium hydroxide, filtered and extracted with ethyl acetate. The organic layer was dried with anhydrous potassium carbonate, filtered, and then evaporated. Recrystallization from ethyl acetate afforded 0.7 g (46% yield) (S)-3-[(1-azabicyclo[2.2.2]oct-3-yl)aminocarbonyl]-1,2-dimethylindole, m.p. 176°-177° C.; [α]D25 -51.90 (c 0.92, CHCl3). Anal. for C18H23N3O: Calcd: C, 72.70; H, 7.79; N, 14.13. Found: C, 72.75; H, 7.89; N, 14.15.

Provenance & Evidence