Hydroxyphenylacetic acid → 2-((4-Carboxymethylphenoxy)methyl)benzoic acid

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Reaction Steps

Those 6,11-dihydro-11-oxodibenz[b,e]oxepins of this invention wherein the substituent at the 2-position is 4-hydroxy-3-pyrrolin-2,5-dione-3-yl may be prepared according to the following general reaction scheme: ##STR9## wherein R2 and R3 are as previously defined, by treating an appropriately substituted R2 and/or R3 phthalide with the disodium salt of p-hydroxyphenylacetic acid at 170°-250° C. for 2-3 hours to obtain the corresponding 4-(2-carboxybenzyloxy)phenylacetic acid. The disodium salt of p-hydroxyphenylacetic acid is formed by treating the acid with aqueous sodium hydroxide and evaporating the mixture to dryness. The phthalide is then added and the reaction is carried out as described above. The carboxybenzyloxyphenylacetic acid so produced then is cyclized by stirring with trifluoroacetic anhydride in a pressure bottle at 70°-80° C. for 1-3 hours. The intermediate R2 and/or R3 substituted 6,11-dihydro-11-oxodibenzo[b,e]oxepin-2-acetic acid trifluoroacetic acid mixed anhydride then is treated with base and acidified in order to obtain the free acid. The free acid then is treated with thionyl chloride followed by ammonia to form the corresponding acetamide which is treated with diethyl oxalate in dimethylformamide in the presence of potassium t-butoxide to form the desired R2 and/or R3 substituted 2-(4-hydroxy-Δ3 -pyrrolin-2,5-dione-3-yl)-6,11-dihydro-11-oxodibenz[b,e]oxepin of formula VI.

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