Triethylamine → HCID 68983260, compound

Participants

Reaction Conditions

Reaction Steps

2-(2-Phenylindolizin-1-yl)acetamide (1.0 g, 40 mmol) was dissolved in dichloroethane (35 mL) containing triethylamine (0.65 mL). To the stirred solution was added propionyl chloride (0.70 mL). The reaction mixture was heated in an oil bath (70° C.) over the weekend. After cooling, the reaction mixture was diluted with methylene chloride and water. The phases were separated and the aqueous phase was extracted with methylene chloride 3 times. Evaporation of the combined organic layers gave a residue which was purified by column chromatography on silica gel eluting with 1.0-1.2% methanol in methylene chloride to give 115 mg of 1-cyanomethyl-3-propionyl-2-phenylindolizine. The cyanomethyl keto indolizine was reduced to the title compound with lithium aluminum hydride (150 mg) in ethyl ether under reflux in a nitrogen atmosphere overnight. After cooling the reaction mixture was quenched with Rochelle salt and stirred to give a solution. The phases were separated and the aqueous phase was extracted with ether and then made basic with 2.5 N NaOH. The crude product was extracted into methylene chloride and the solvent removed under reduced pressure to give a residue which was purified on silica gel eluting with 9% methanol in methylene chloride to give 70 mg of the free base of the title compound. The free base was dissolved in ethanol to which an ethanolic solution of 70 mg of fumaric acid was added. The solution was evaporated and the residue was recrystallized from methyl ethyl ketone to give the fumaric acid salt of the title compound, mp: 169-172° C.; MS [M+H]+ 279 m/z; Microanalysis was consistent for C19H22N2+C4H4O4+0.7 H2O

Provenance & Evidence