Methanol → Methyl 4-iodo-3-nitrobenzoate

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Reaction Steps

The required starting material, 4-iodo-3-nitrobenzoic acid, can be prepared as described in Tetrahedron, 61, 2005, 10113-10121, or by any other suitable method. The conversion of 4-iodo-3-nitrobenzoic acid to its methyl ester using sulfuric acid and methanol is described in U.S. 2007/0135485 A1 (section [0255], page 30). The method involves reacting a methanolic solution of 4-iodo-3-nitrobenzoic acid with sulfuric acid, neutralizing the acid with sodium bicarbonate, removal of methanol, diluting with water and extracting with diethyl ether, to obtain an oily product, which was subjected to chromatography to get 4-iodo-3-nitro benzoic methyl ester as a solid in 77% yield. Diethyl ether is not a suitable solvent on an industrial scale because of its high inflammability. Also column chromatography for purification in large scale is not desirable. Hence, we have modified the reported procedure. We have found that methyl tert-butyl ether (MTBE) is a better solvent for extraction which gives the product as a solid directly without any need for chromatographic purification (98.5% HPLC) and in high yield (85%).

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