Sodium Methoxide → 6-(benzylthio)-1-(4-bromo-5-chloro-2-methoxyphenyl)quinolin-2(1H)-one

HRID 1504494Notes

Reaction equation

HRID 1504494 reaction equation
[CH2:1]([S:8][C:9]1[CH:10]=[CH:11][C:12]([NH:22][C:23]2[CH:28]=[C:27]([Cl:29])[C:26]([Br:30])=[CH:25][C:24]=2[O:31][CH3:32])=[C:13](/[CH:15]=[CH:16]/[C:17](OCC)=[O:18])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[O-].[Na+]>CO>[CH2:1]([S:8][C:9]1[CH:14]=[C:13]2[C:12](=[CH:11][CH:10]=1)[N:22]([C:23]1[CH:28]=[C:27]([Cl:29])[C:26]([Br:30])=[CH:25][C:24]=1[O:31][CH3:32])[C:17](=[O:18])[CH:16]=[CH:15]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 117746875(E)-ethyl 3-(5-(benzylthio)-2-((4-bromo-5-chloro-2-methoxyphenyl)amino)phenyl)acrylate

Product 1

HCID 1177373026-(benzylthio)-1-(4-bromo-5-chloro-2-methoxyphenyl)quinolin-2(1H)-oneYield 75.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

A flask was charged with (E)-ethyl 3-(5-(benzylthio)-2-((4-bromo-5-chloro-2-methoxyphenyl)amino)phenyl)acrylate (73.2 g, 137 mmol) and MeOH (687 ml) to give a yellow suspension. Sodium methoxide (25 wt % in MeOH) (15.01 ml, 54.9 mmol) was added and a reflux condenser was attached. The flask was lowered into a 70° C. heating bath and stirred at 70° C. for 18 h. The mixture was cooled to rt and poured through a 3 inch silica plug to remove black particulates. The product that was crashed out on the silica plug was washed through the plug with DCM. The mother liquor was concentrated to half its volume, then IPA (500 mL) was added and the solution concentrated again. An additional 500 mL of IPA was added and a tan solid precipitated. The tan solid was collected by vacuum filtration to give 6-(benzylthio)-1-(4-bromo-5-chloro-2-methoxyphenyl)quinolin-2(1H)-one (50.34 g, 103 mmol, 75% yield) as a dark tan powdery solid. m/z (ESI) 486.0 (M+H)+.

Workup

  1. customto give a yellow suspension
  2. customa reflux condenser was attached
  3. customwas lowered into a 70° C.
  4. temperatureheating bath
  5. temperatureThe mixture was cooled to rt
  6. additionpoured through a 3 inch silica plug
  7. customto remove black particulates
  8. washwas washed through the plug with DCM
  9. concentrationThe mother liquor was concentrated to half its volume
  10. additionIPA (500 mL) was added
  11. concentrationthe solution concentrated again
  12. additionAn additional 500 mL of IPA was added
  13. customa tan solid precipitated
  14. filtrationThe tan solid was collected by vacuum filtration

Sources & evidence

ORD record
ord-8eeb3e9e255f4642afda75e56b84603f
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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