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

HRID 1504368Notes

Reaction equation

HRID 1504368 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]=[CH:23][C:22]([Br:25])=[CH:21][C:20]=1[O:26][CH3:27])[C:14](=[O:28])[CH:13]=[CH:12]2)C1C=CC=CC=1.ClN1C(C)(C)C(=[O:37])N(Cl)C1=O.[F:40][C:41]1[C:46]([OH:47])=[C:45]([F:48])[C:44]([F:49])=[C:43]([F:50])[C:42]=1[F:51].C(N(CC)CC)C.[OH2:59]>C(Cl)Cl.CC(O)=O>[Br:25][C:22]1[CH:23]=[CH:24][C:19]([N:15]2[C:16]3[C:11](=[CH:10][C:9]([S:8]([O:47][C:46]4[C:41]([F:40])=[C:42]([F:51])[C:43]([F:50])=[C:44]([F:49])[C:45]=4[F:48])(=[O:37])=[O:59])=[CH:18][CH:17]=3)[CH:12]=[CH:13][C:14]2=[O:28])=[C:20]([O:26][CH3:27])[CH:21]=1

Participants

8

Reactant 5

HCID 962WaterHCID 83601,3-Dichloro-5,5-dimethylhydantoin2×HCID 8471TriethylamineHCID 13041PentafluorophenolHCID 1177371856-(benzylthio)-1-(4-bromo-2-methoxyphenyl)quinolin-2(1H)-one

Product 1

HCID 117737057(S)-Perfluorophenyl 1-(4-bromo-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonateYield 80%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 6-(benzylthio)-1-(4-bromo-2-methoxyphenyl)quinolin-2(1H)-one (57.89 g, 128 mmol) in 400 mL DCM was treated with 15 mL HOAc and 10 mL water and was cooled to 0° C. 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione (25.2 g, 128 mmol) was added portionwise. After stirring for 30 minutes, an additional 0.5 equvalents of 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione was added portionwise. After stirring for an additional 30 minutes, the reaction mixture was then treated with pentafluorophenol (16.06 mL, 154 mmol) and was maintained at 0° C. triethylamine (71.3 mL, 512 mmol) was added dropwise via addition funnel over 30 minutes. The reaction mixture was diluted with DCM, washed with water, and the organics were dried over MgSO4 and concentrated. The crude residue was triturated with IPA then dried and collected yielding perfluorophenyl 1-(4-bromo-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (58.7 g, 102 mmol, 80% yield) as a mixture of atrope isomers. m/z (ESI) 576.0 (M+H)+. The atropisomers were separated using supercritical fluid chromatography (SFC). The column used was (S,S) Whelk-O, 2×15 cm. The mobile phase was run under isocratic conditions; CO2 with 50% isopropanol to afford product as an off-white solid. First atropisomer (peak 1): (P)-perfluorophenyl 1-(4-bromo-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (26.6 g, 46.2 mmol, 36.1% yield) 1H NMR (ACETONITRILE-d3) □: 8.33 (d, J=2.2 Hz, 1H), 8.01 (d, J=9.4 Hz, 1H), 7.85 (dd, J=9.1, 2.2 Hz, 1H), 7.47 (d, J=2.1 Hz, 1H), 7.39 (dd, J=8.3, 2.0 Hz, 1H), 7.23 (d, J=8.3 Hz, 1H), 6.86 (d, J=9.0 Hz, 1H), 6.81 (d, J=9.7 Hz, 1H), 3.73 (s, 3H). m/z (ESI) 576.0 (M+H)+. Second atropisomer (peak 2): (M)-perfluorophenyl 1-(4-bromo-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (26.6 g, 46.2 mmol, 36.1% yield). 1H NMR (ACETONITRILE-d3): 8.33 (d, J=2.2 Hz, 1H), 8.00 (d, J=9.6 Hz, 1H), 7.85 (dd, J=9.0, 2.3 Hz, 1H), 7.46 (d, J=2.0 Hz, 1H), 7.38 (dd, J=8.3, 2.1 Hz, 1H), 7.22 (d, J=8.3 Hz, 1H), 6.86 (d, J=9.0 Hz, 1H), 6.81 (d, J=9.6 Hz, 1H), 3.72 (s; 3H). m/z (ESI) 576.0 (M+H)+.

Workup

  1. stirringAfter stirring for an additional 30 minutes
  2. additionwas added dropwise via addition funnel over 30 minutes
  3. washwashed with water
  4. dry with materialthe organics were dried over MgSO4
  5. concentrationconcentrated
  6. customThe crude residue was triturated with IPA
  7. customthen dried
  8. customcollected

Sources & evidence

ORD record
ord-629929669c7b42eeb7ad863ef67c994a
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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