Acetic Acid → 5-{[3,5-Bis(1,1-dimethylethyl)-4-hydroxyphenyl]}-methylene-2-thioxo-4-thiazolidinone

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Reaction Steps

Form I is the predominant crystal form at temperatures from about 60° C. to about 155° C. Substantially pure Form I can be obtained in a laboratory setting by refluxing 3,5-di-tert-butyl-4-hydroxybenzaldehyde with rhodanine in glacial acetic acid using fused sodium acetate as a catalyst to form 5-{[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]}-methylene-2-thioxo-4-thiazolidinone. The resultant 2-thioxo-4-thiazolidinone can then be reduced with hydrogen in the presence of palladium on carbon. The product is isolated by chromatography, and the solvent is removed to afford Form I Tazofelone. In an alternate preparation, 5-{[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]}-methylene-2-thioxo-4-thiazolidinone can be refluxed with diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate and activated silica gel to form (±)-5-{[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-methyl}-2-thioxo-4-thiazolidinone. The methyl-2-thioxo-4-thiazolidinone can then be reduced using hydrogen in the presence of palladium on carbon.

Provenance & Evidence