Sodium Methoxide → HCID 117737085, compound

HRID 1504506Notes

Reaction equation

HRID 1504506 reaction equation
[CH2:1]([S:8][C:9]1[CH:10]=[CH:11][C:12]([NH:22][C:23]2[CH:28]=[C:27]([Br:29])[C:26]([Cl: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]([Br:29])[C:26]([Cl: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 117746885HCID 117746885, compound

Product 1

HCID 117737085HCID 117737085, compoundYield 43.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
70 °C

Procedure

A RBF was charged with (E)-ethyl 3-(5-(benzylthio)-2-((5-bromo-4-chloro-2-methoxyphenyl)amino)phenyl)acrylate (6.80 g, 12.76 mmol) and MeOH (63.8 ml) to give a yellow suspension. Sodium methoxide, 25 wt % solution in methanol (10.21 ml, 5.10 mmol) was added, the RBF was fitted with a reflux condenser and the reaction was heated at 70° C. overnight. The reaction was cooled to RT and concentrated in vacuo. The crude material was concentrated onto silica gel and purified via MPLC, eluting with 50% ethyl acetate in heptanes (with 10% DCM additive) (isocratic). The impure material retrieved from column chromatography was dissolved in DCM and further purified via SCX column (product eluted with the methanol wash). The methanol filtrate was concentrated in vacuo and then the solids were triturated in IPA, filtered over a frit washing with minimal IPA to yield 6-(benzylthio)-1-(5-bromo-4-chloro-2-methoxyphenyl)quinolin-2(1H)-one (2.71 g, 5.57 mmol, 43.6% yield) as a beige solid. m/z (ESI) 486.0 (M+H)+.

Workup

  1. customto give a yellow suspension
  2. customthe RBF was fitted with a reflux condenser
  3. temperatureThe reaction was cooled to RT
  4. concentrationconcentrated in vacuo
  5. concentrationThe crude material was concentrated onto silica gel
  6. custompurified via MPLC
  7. washeluting with 50% ethyl acetate in heptanes (with 10% DCM additive) (isocratic)
  8. dissolutionwas dissolved in DCM
  9. customfurther purified via SCX column (product
  10. washeluted with the methanol
  11. washwash)
  12. concentrationThe methanol filtrate was concentrated in vacuo
  13. customthe solids were triturated in IPA
  14. filtrationfiltered over a frit
  15. washwashing with minimal IPA

Sources & evidence

ORD record
ord-24e814b3e7894103880040b17b13f099
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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