Dichloromethane → (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-1-methyl-alpha-oxo-3-indoleacetamide

Participants

Reaction Steps

(S)-3-amino-1-azabicyclo[2.2.2]octane dihydrochloride salt (7.5 g; 37.5 mmol) and sodium hydroxide (2.0 g; 50.0 mmols) were dissolved in 50 ml of water. The solution was cooled in an ice bath and 100 ml of methylene chloride was added. The mixture was stirred while approximately one third of a solution containing 1-methy-α-oxo-3-indoleacetyl chloride (10.8 g; 48.7 mmol) was added in a dropwise fashion, after which additional sodium hydroxide (3.0 g; 75.0 mmol) in 20.0 ml of water was mixed in. The remaining 1-methy-α-oxo-3-indoleacetyl chloride was then added and the reaction mixture was stirred for 10 minutes. The aqueous layer was then separated from the organic phase and rinsed with methylene chloride. The combined organic phase was dried over potassium carbonate. Filtration and evaporation of the solvent resulted in 5.1 g of crude product. The crude product was purified by chromatography (silica gel 60; 7% MeOH in CH2Cl2 containing approximately 0.5 % NH4OH) to yield 3.6 g (11.5 mmmol) of (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-1-methyl-α-oxo-3-indoleacetamide, m.p. 186°-187° C., [α]D25 -41° (CHCl3).

Provenance & Evidence