Sulfuric Acid → Ethyl 5-sulfanyl-1,3,4-thiadiazole-2-carboxylate

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Reaction Conditions

Reaction Steps

Scheme 1 shows a synthetic method that may be used to prepare compounds of formula I-III. First, hydrazino-oxo-acetic acid ethyl ester 1 (prepared by the method of Berdinskii, I. S.; Maslivets, A. N. Hydrazides of disubstituted glycolic acids. Zh. Org. Khim. (1982), 18(9), 1839-43) is treated with carbon disulfide (excess) and KOH (1.0 equiv.) in ethanol at 0° C. to give 2. Treatment of 2 with cold (excess) sulfuric acid for 20 minutes followed by heating to 55° C. for 1 hour gives 5-mercapto-[1,3,4]-thiadiazole-2-carboxylic acid ethyl ester which is then treated with ethyl iodide and potassium carbonate in ethanol/water at room temperature to give 3. Heating compound 4 in the presence of benzylamine gives the amide, which is oxidized to the sulfone 5 with m-chloroperbenzoic acid (2.5 equiv) in chloroform or methylene chloride at room temperature. Treatment of 5 with 3-oxo-pentanoic acid methyl ester and excess sodium hydride in refluxing tert-butanol for 48 hours gives 6 after flash silica purification.

Provenance & Evidence