Nitrogen → HCID 11665798, compound

Participants

Reaction Steps

2-(2-ethylindolizin-1-yl)acetamide (1.0 g, 5 mmol) was dissolved in dichloroethane (30 mL) to which was added triethylamine (TEA, 0.65 mL) N,N-dimethylaminopyridine (DMAP, 60 mg) and propionyl chloride (0.7 mL). The reaction mixture was heated under reflux in a N2 atmosphere overnight. The cooled reaction mixture was partitioned between water and methylene chloride. The phases were separated and the aqueous phase was extracted with methylene chloride 3 times. The organic layers were combined and evaporated to give a residue which was purified by silica gel column chromatography eluting with ethyl acetate. A total of 600 mg of 2-(2-ethyl-3-propionylindolizin-1-yl)-acetamide was recovered. 2-(2-ethyl-3-propionylindolizin-1-yl)-acetamide (400 mg, 1.5 mmol) was suspended in anhydrous ethyl ether to which lithium aluminum hydride (LAH, 380 mg) was added. The suspension was heated under reflux in a N2 atmosphere overnight. After cooling to room temperature the reaction mixture was partitioned between ether and aqueous Rochelle salt. After stirring for 1 h, the phases were separated. The aqueous phase was extracted with ether 2 times. Evaporation of the combined organic layers gave a residue which was purified on silica gel eluting with 1 L each of 5%, 10%, 12% methanol in methylene chloride containing 4 mL of conc. NH4OH. The title compound was isolated (85 mg), dissolved in ethanol and treated with an ethanolic solution of fumaric acid (65 mg). The ethanol was evaporated and the residue was recrystallized from methyl ethyl ketone (MEK) to give the title compound as the fumaric acid salt, mp: 154-158° C.; Mass sSpectrum [M+H]+ 231 m/z.

Provenance & Evidence