Water → 2-(Cyclopropylamino)-5-methyl-3,4-thiophenedicarboxylic acid, 3-ethyl 4-methyl ester

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Reaction Steps

To a solution of (triphenylphosphoranylidene)-acetic acid ethyl ester (15 g) in anhydrous tetrahydrofuran (100 ml) was added isothiocyanato-cyclopropane (4.4 g) and the mixture was refluxed under a nitrogen atmosphere for 20 hr. After allowing to cool to ambient temperature the reaction mixture was cooled to −78° C. and then a solution of 3-bromo-2-oxo-butanoic acid methyl ester (8.7 g) in anhydrous tetrahydrofuran (10 ml) was added. The resulting mixture was allowed to warm to ambient temperature and then refluxed for 20 hr., then ambient temperature for 2 days. The reaction was poured into water and extracted with diethyl ether. The collected organic extract was dried over magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography over silica, eluting with i-hexane/ethyl acetate (95:5) then triturated with i-hexane/diethyl ether (8:2) to give the sub-title compound as a solid (7.5 g).

Provenance & Evidence