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

HRID 1473494Notes

Reaction equation

HRID 1473494 reaction equation
C(S[C:9]1[CH:10]=[N:11][C:12]2[C:17]([CH:18]=1)=[CH:16][CH:15]=[N:14][C:13]=2[C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][C:20]=1[O:29][CH3:30])C1C=CC=CC=1.ClN1C(C)(C)C(=O)N(Cl)C1=O.[S:42](Cl)(Cl)(=[O:44])=[O:43].[F:47][C:48]1[C:53]([F:54])=[C:52]([F:55])[C:51]([F:56])=[C:50]([F:57])[C:49]=1[OH:58].C(N(CC)CC)C>CCOC(C)=O.O.C(O)(=O)C.C(#N)C>[CH3:30][O:29][C:20]1[CH:21]=[C:22]([C:25]([F:27])([F:28])[F:26])[CH:23]=[CH:24][C:19]=1[C:13]1[N:14]=[CH:15][CH:16]=[C:17]2[C:12]=1[N:11]=[CH:10][C:9]([S:42]([O:58][C:49]1[C:48]([F:47])=[C:53]([F:54])[C:52]([F:55])=[C:51]([F:56])[C:50]=1[F:57])(=[O:44])=[O:43])=[CH:18]2

Participants

10

Reactant 5

HCID 83601,3-Dichloro-5,5-dimethylhydantoinHCID 8471TriethylamineHCID 13041PentafluorophenolHCID 24648Sulfuryl chlorideHCID 866875483-(Benzylthio)-8-(2-methoxy-4-(trifluoromethyl)phenyl)-1,7-naphthyridine

Product 1

HCID 86687549Perfluorophenyl 8-(2-methoxy-4-(trifluoromethyl)phenyl)-1,7-naphthyridine-3-sulfonateYield 76%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

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)+.

Workup

  1. temperatureThe resulting solution was cooled in an ice water bath
  2. waitAfter 15 min LC/MS indicated complete
  3. extractionextracted with water
  4. extractionThe aqueous phase was extracted with EtOAc
  5. dry with materialthe combined organics were dried with Na2SO4
  6. filtrationfiltered
  7. customdried under reduced pressure
  8. customthe crude oil purified with a 40 g silicycle HP column (SiliCycle, Inc. Quebec City, Canada)

Sources & evidence

ORD record
ord-16dab7c4f87c4c8d9fd55c10e88efbfa
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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