Citric Acid → tert-butyl N-[4-(3-bromo-5-hydroxyphenyl)sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

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Reaction Steps

Following the procedure and workup in Example 14: step f, the 4-(3-bromo-5-tert-butoxy-benzenesulfonyl)-5-methylsulfanyl-thiophene-2-carboxylic acid methyl ester ((Example 12: step c) 1.48 g, 3.1 mmol) was converted to the amidine (40 mL of dimethylaluminum amide reagent) with concomitant removal of the tert-butyl ether. A portion of the crude amidine (800 mg) was dissolved in DMF and di-tert-butyl dicarbonate (436 mg, 2 mmol), diisopropylethylamine (350 μL, 2 mmol), and DMAP (50 mg) were added. After stirring for 16 h, the solution was poured into EtOAc (60 mL) and citric acid (20 mL). The layers were separated and the organic layer was further extracted with citric acid (10 mL), NaHCO3 (2×20 mL), water (5×10 mL), and brine (30 mL). After drying over sodium sulfate and removal of solvent in vacuo, the residue was dissolved in MeOH and solid K2CO3 was added. The mixture was stirred overnight, the solution was filtered, and the solvent was removed in vacuo. Purification of the residue by SiO2 flash chromatography yielded the title compound (80 mg, 0.158 mmol).

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