Water → Perfluorophenyl 1-(4-bromo-5-fluoro-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate

HRID 1504464Notes

Reaction equation

HRID 1504464 reaction equation
C([S:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]([C:19]1[CH:24]=[C:23]([F:25])[C:22]([Br:26])=[CH:21][C:20]=1[O:27][CH3:28])[C:14](=[O:29])[CH:13]=[CH:12]2)C1C=CC=CC=1.ClN1C(C)(C)C(=[O:38])N(Cl)C1=O.[F:41][C:42]1[C:47]([OH:48])=[C:46]([F:49])[C:45]([F:50])=[C:44]([F:51])[C:43]=1[F:52].CCN(CC)CC.[OH2:60]>C(#N)C.C(O)(=O)C>[Br:26][C:22]1[C:23]([F:25])=[CH:24][C:19]([N:15]2[C:16]3[C:11](=[CH:10][C:9]([S:8]([O:48][C:47]4[C:42]([F:41])=[C:43]([F:52])[C:44]([F:51])=[C:45]([F:50])[C:46]=4[F:49])(=[O:38])=[O:60])=[CH:18][CH:17]=3)[CH:12]=[CH:13][C:14]2=[O:29])=[C:20]([O:27][CH3:28])[CH:21]=1

Participants

8

Reactant 5

HCID 962Water2×HCID 83601,3-Dichloro-5,5-dimethylhydantoinHCID 8471TriethylamineHCID 13041PentafluorophenolHCID 1177370446-(benzylthio)-1-(4-bromo-5-fluoro-2-methoxyphenyl)quinolin-2(1H)-one

Product 1

HCID 117736986Perfluorophenyl 1-(4-bromo-5-fluoro-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonateYield 60%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 6-(benzylthio)-1-(4-bromo-5-fluoro-2-methoxyphenyl)quinolin-2(1H)-one (250.0 g, 531.5 mmol, 1.0 equiv) in acetonitrile (2.5 L) were added acetic acid (200 mL) and water (130 mL). The resulting mixture was cooled to 0° C. and 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione (188.5 g, 956.7 mmol, 1.8 equiv, Aldrich) was added portion-wise over 20 min keeping the internal temperature below 5° C. The resulting suspension was stirred at 0-5° C. under nitrogen for 45 min. Then a solution of pentafluorophenol (127.2 g, 690.95 mmol, 1.3 equiv, Apollo) in acetonitrile (200 mL) was added over 5 min followed by NEt3 (307.7 mL, 2.12 mol, 4.0 equiv) over 20 min keeping the internal temperature below 5° C. The mixture was continued to be stirred at 0-5° C. for 30 min. Water (4.0 L) was added and extracted with ethyl acetate (2×2.0 L). The organic layer was washed with brine (1.0 L), dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude which was purified by stirring with isopropyl alcohol:hexanes (1:1, 1.0 L) and filtered to obtain perfluorophenyl 1-(4-bromo-5-fluoro-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (190 g, 60%) as white solid. TLC solvent system: 30% ethyl acetate in pet ether, Product's Rf 0.4. MS (ESI, positive ion) m/z; 594.2 (M+1). 1H-NMR (400 MHz, DMSO) δ 8.60 (d, J=2.0 Hz, 1H), 8.26 (d, J=9.8 Hz, 1H), 7.95 (dd, J=2.2, 9.1 Hz, 1H), 7.70 (t, J=8.6 Hz, 2H), 6.95-6.88 (m, 2H), 3.72 (s, 3H).

Workup

  1. customthe internal temperature below 5° C
  2. customthe internal temperature below 5° C
  3. stirringto be stirred at 0-5° C. for 30 min
  4. extractionextracted with ethyl acetate (2×2.0 L)
  5. washThe organic layer was washed with brine (1.0 L)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto obtain the crude which
  10. customwas purified
  11. stirringby stirring with isopropyl alcohol:hexanes (1:1, 1.0 L)
  12. filtrationfiltered

Sources & evidence

ORD record
ord-0b3debafe4514ed2b21afe463204bd75
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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