Nitromethane → 3-[3-(4-Fluoro-phenyl)-5-methyl-isoxazole-4-carbonyl]-1H-indole-6-carboxylic acid methyl ester

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Reaction Steps

To a stirred solution of 1.75 g (10 mmol) methyl indole-6-carboxylate (commercially available) in 15 mL of dry CH2Cl2 under argon at 0° C. was added 1.41 mL (12 mmol) of SnCl4 in one portion. After removing the ice-bath, the mixture was stirred for 40 min at room temperature and then 2.39 g (10 mmol) of 3-(4-fluoro-phenyl)-5-methyl-isoxazole-4-carboxylic acid chloride (Prepared from the corresponding acid according to: J. Agric. Food Chem. 1995, 43, 219-228.) in 5 mL of CH2Cl2 was added at 0° C. followed by the addition of 15 mL of nitromethane in one portion. The mixture was stirred for 15 minutes at 0° C., after which 50 mL of ice-water was added to quench the reaction. The organic phase was separated and the aqueous solution was extracted with CH2Cl2 (2×20 mL). The combined extracts were washed with brine (30 mL), dried over Na2SO4, and evaporated to give 3.5 g of crude product (purity ˜30%, LCMS) as brown semi-solid. The crude product was further washed with ethyl acetate to give 0.85 g of the title compound in 23% yield as a light-yellow powder. (m/e): 379.2 (MH+; 100%).

Provenance & Evidence