Hydrochloric Acid → Ethyl 4-(3-(benzyloxycarbonylamino)-2-methylphenyl)-7-(tetrahydrofuran-3-yloxy)-9H-pyrido[3,4-b]indole-1-carboxylate

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Reaction Steps

To a solution of benzyl 3-(2-amino-1-(6-(tetrahydrofuran-3-yloxy)-1H-indol-3-yl)ethyl)-2-methylphenylcarbamate (0.678 g, 1.396 mmol) and ethyl 2-oxoacetate in toluene (50%) (0.554 mL, 2.79 mmol) at room temperature was added hydrogen chloride in 1,4-dioxane (4.0 M) (0.419 mL, 1.676 mmol). The mixture was stirred room temperature for 16 hr. The volatiles were removed under vacuum. The residue was diluted with water (50 mL), basified with NaHCO3 solution to pH 10, and extracted with ethyl acetate (4×50 mL). The combined extract was washed with brine (40 ml), dried over anhydrous MgSO4, and concentrated to dryness under vacuum. To the residue were added p-xylene (60 mL) and 10% Pd/C (0.46 g), and the mixture was heated at 125° C. under an ambient atmosphere for 4.5 hr. The solid phase was removed by suction filtration. The filtrate was diluted with ethyl acetate (120 ml), washed with brine (40 ml), and dried over anhydrous MgSO4. The desired product (0.240 g, 0.424 mmol, 30.4% yield) was isolated by ISCO (40 g silica gel, solid loading, 15-35% ethyl acetate/CH2Cl2).

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