1,3-Dichloro-5,5-dimethylhydantoin → Perfluorophenyl 8-(2-methoxy-4-(trifluoromethyl)phenyl)-1,7-naphthyridine-3-sulfonate

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Reaction Steps

To a vial charged with 3-(benzylthio)-8-(2-methoxy-4-(trifluoromethyl)phenyl)-1,7-naphthyridine (0.295 g, 0.692 mmol) was added acetonitrile (3.26 ml), acetic acid (0.122 ml) and water (0.081 ml). The resulting solution was cooled in an ice water bath prior to the addition of 1,3-dichloro-5,5-dimethylhydantoin (0.068 ml, 0.519 mmol). After 90 min of stirring (ice melt) LC/MS indicated fairly clean conversion to sulfonyl chloride. To the mixture was added 2,3,4,5,6-pentafluorophenol (0.036 ml, 0.346 mmol) followed by the drop wise addition of triethylamine (0.193 ml, 1.384 mmol). After 15 min LC/MS indicated complete conversion to product. The yellow solution was diluted with EtOAc and extracted with water. The aqueous phase was extracted with EtOAc and the combined organics were dried with Na2SO4, filtered, dried under reduced pressure and the crude oil purified with a 40 g silicycle HP column (SiliCycle, Inc. Quebec City, Canada) ramping EtOAc in heptane (0 to 65%, 5% DCM throughout) to afford perfluorophenyl 8-(2-methoxy-4-(trifluoromethyl)phenyl)-1,7-naphthyridine-3-sulfonate (0.145 g, 0.263 mmol, 76% yield) as a white foam. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.30 (s, 1H) 7.45 (dt, J=7.78, 0.81 Hz, 1H) 7.60-7.65 (m, 1H) 7.89 (d, J=5.77 Hz, 1H) 8.90 (d, J=2.35 Hz, 1H) 8.95 (d, J=5.58 Hz, 1H) 9.36 (d, J=2.35 Hz, 1H). m/z (ESI) 551.2 (M+H)+.

Provenance & Evidence