1,3-Dichloro-5,5-dimethylhydantoin → HCID 86687720, compound

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Reaction Steps

A round-bottom flask was charged with 7-(benzylthio)-4-(2-methoxyphenyl)phthalazin-1(2H)-one (150 mg, 0.401 mmol), acetonitrile (3770 μl), acetic Acid (141 μl), and water (94 μl) to give a yellow suspension. The mixture was sonicated to give a yellow suspension. The flask was cooled in an ice-bath for 30 min, then 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione (158 mg, 0.801 mmol) was added in one portion. After 20 min, LCMS showed SM (m/z=375), sulfoxide (m/z=391), sulfonyl chloride (m/z=352), Cl-sulfonyl chloride (m/z=385,387). DCM (0.5 mL) was added to give a yellow solution. After 1.5 h, an orange suspension was formed. LCMS showed mainly 1-(5-chloro-2-methoxyphenyl)-4-oxo-3,4-dihydrophthalazine-6-sulfonyl chloride. Then, 2,3,4,5,6-pentafluorophenol (147 mg, 0.801 mmol) was added at 0° C., followed by drop wise addition of triethylamine (223 μl, 1.602 mmol) via an addition funnel. After 15 min, LCMS showed mainly PFP sulfonate product. The mixture was diluted with EtOAc (20 mL) and washed with water (2×10 mL), washed with brine, and dried over sodium sulfate. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 50% EtOAc in hexanes, to provide perfluorophenyl 1-(5-chloro-2-methoxyphenyl)-4-oxo-3,4-dihydrophthalazine-6-sulfonate (128 mg, 60.0% yield) as white solid. HMBC connectivities and ROESY cross-peaks confirmed the structure of perfluorophenyl 1-(5-chloro-2-methoxyphenyl)-4-oxo-3,4-dihydrophthalazine-6-sulfonate (128 mg, 60% yield). Specifically, the chlorine was para to the methoxy substitutent. m/z (ESI) 533.0 (M+H)+.

Provenance & Evidence