Methanol → Methyl 5-hydroxy-4-methoxy-2-nitrobenzoate

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Reaction Conditions

Reaction Steps

5-hydroxy-4-methoxy-2-nitrobenzoic acid (31.9 g, 0.15 mol, 1.0 eq) and 2-methyltetrahydrofuran (200 mL) are charged into a glass reactor under nitrogen. The solution is stirred and jacket temp is set to 20° C. Oxalyl chloride (24 g, 0.19 mol, 1.25 eq) is added at a rate that the internal temperature is below 25° C. The reaction mixture is stirred for 1-2 hour at 20° C., and cooled to 15° C. Then, anhydrous MeOH (60 ml, 1.5 mol, 10 eq) is added over 15 min, and the reaction temperature is maintained below 25° C. during addition. The reaction mixture is stirred for 2-4 hour at 20° C. until HPLC sample shows complete conversion. Na2CO3 aqueous solution (1 M, 100 ml) is added to the reaction mixture. Layers are separated. The upper organic layer is distilled under vacuum to minimum volume. The dark brown residue is stirred in 100 mL mixed solvent of toluene/hexane (v/v, 2:1) to give a suspension. The slurry is filtered. The solid is dried under vacuum to provide the desired product, methyl 5-hydroxy-4-methoxy-2-nitrobenzoate (31.3 g, 92% yield).

Provenance & Evidence