Hydrochloric Acid → Ethyl 4-(2-fluorophenyl)-7-morpholino-9H-pyrido[3,4-b]indole-1-carboxylate

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Reaction Steps

To a solution of 2-(2-fluorophenyl)-2-(6-morpholino-1H-indol-3-yl)ethanamine (0.181 g, 0.533 mmol) and ethyl 2-oxoacetate in toluene (50%) (0.233 mL, 1.173 mmol) in 1,4-dioxane (18 mL) at room temperature was added hydrogen chloride (4 N in 1,4-dioxane) (0.267 mL, 1.067 mmol). The solution turned heterogeneous and it was stirred at room temperature for 16 hr. The volatiles were removed under vacuum. The residue was diluted with water (20 mL), basified with saturated NaHCO3 solution to pH 10, and extracted with ethyl acetate (3×30 mL). The combined extract was washed with brine (25 ml), dried over anhydrous MgSO4, and concentrated to dryness under vacuum. To the residue were added toluene (10 mL) and 10% Pd/C (0.3 g), and the mixture was heated at 140° C. under an ambient atmosphere for 4.5 hr. The solid phase was removed by suction filtration. The filtrate was diluted with ethyl acetate (100 ml), washed with brine (25 ml), and dried over anhydrous MgSO4. The desired product (94 mg, 0.222 mmol, 41.6% yield) was isolated with ISCO (24 g silica gel, 30-60% ethyl acetate/hexane) as a tan solid.

Provenance & Evidence