Chloroform → Methyl 5-nitro-2-(2-methoxy-6-methoxymethoxyphenyl)-benzoate

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Reaction Conditions

Reaction Steps

A solution of 1-methoxy-3-methoxymethoxy benzene (3.62 g., 21.55 mmole), prepared as described in J. Med. Chem. 1995, 38, 1437-1445, in THF (15 mL) at −30° C. was treated with n-butyllithium (8.28 ml. of 2.5 M in hexane, 20.69 mmole), stirred for 1 hour at 25° C., cooled to 0° C., treated with anhydrous zinc chloride beads (3.5 g, 25.67 mmole), stirred for 2 hours at 25° C., treated with a solution of methyl-2-bromo-5-nitrobenzoate (5.0 g, 19.23 mmol) in THE (20 mL) and bis(triphenylphosphine)palladium dichloride (600 mg), stirred at 65° C. for 15 hours, cooled, and treated with chloroform and aqueous KHCO3. The precipitated zinc salts were filtered, and the water layer was removed, and the organic layer dried over (Na2SO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 8% ethyl acetate in dichloromethane to provide the desired product. MS (ESI(−)Q1MS) m/z 346 (M−H)−.

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