Water → HCID 89690559, compound

HRID 1481859Notes

Reaction equation

HRID 1481859 reaction equation
[CH3:1][O:2][C:3](=[O:27])[C:4]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[C:7]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH3:25])[CH2:15][CH2:14]2)=[CH:6][C:5]=1Cl.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O.[CH2:56]([O:58]/[CH:59]=[CH:60]/B1OC(C)(C)C(C)(C)O1)[CH3:57]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH3:1][O:2][C:3](=[O:27])[C:4]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[C:7]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH3:25])[CH2:15][CH2:14]2)=[CH:6][C:5]=1/[CH:57]=[CH:56]/[O:58][CH2:59][CH3:60]

Participants

8

Reactant 5

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 219739081-Ethoxyethene-2-boronic acid pinacol esterHCID 89690426HCID 89690426, compound

Product 1

HCID 89690559HCID 89690559, compoundYield 76.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent2×

Procedure

In a 10 ml round bottom flask equipped with a magnetic stir bar and a nitrogen inlet, the 2-chloro-5-nitro-4-(4-o-tolyl-piperazin-1-yl)-benzoic acid methyl ester 10a (115.70 mg, 0.30 mmol) was combined dry with the tricyclohexylphosphine (20.00 mg, 0.07 mmol) and was then taken up in clean, dry 1,4-dioxane (0.75 ml, 8.77 mmol) and the mixture was stirred at room temperature under nitrogen atmosphere until all solids were in solution. While that was stirring, the potassium phosphate tribasic (126.00 mg, 0.59 mmol) was dissolved in water (0.50 ml, 27.75 mmol) and once complete dissolution was achieved, the basic solution was added to the stirring dioxane solution. The reaction mixture was then placed under vacuum for 10 min and was then flushed with nitrogen. The 2-((E)-2-ethoxy-vinyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (64.60 mg, 0.33 mmol) was added to the solution, and the system was degassed once more. After flushing the system with nitrogen once more, the tris(dibenzylideneacetone)dipalladium (27.00 mg, 0.03 mmol) was added in one portion and the flask was fitted with a jacketed reflux condenser and the system was purged under vacuum once more. The reaction mixture system was then flushed with nitrogen and warmed to 100° C. The reaction was allowed to stir overnight under nitrogen at elevated temperatures. The reaction was cooled to room temperature and the mixture was filtered through Celite, washing heavily with ethyl acetate. The liquid filtrate was then collected and the solvent was removed under reduced pressure, absorbing the residue onto Celite. The product was then purified using silica gel column chromatography, eluting a gradient of 100% heptanes to 75% ethyl acetate in heptane. The product 2-((E)-2-ethoxy-vinyl)-5-nitro-4-(4-o-tolyl-piperazin-1-yl)-benzoic acid methyl ester 10b (97.10 mg, 0.23 mmol), was isolated as an off-white, slightly yellowish solid. LCMS (m/e)=426 (M+H).

Workup

  1. customIn a 10 ml round bottom flask equipped with a magnetic stir bar and a nitrogen inlet
  2. stirringWhile that was stirring
  3. dissolutiononce complete dissolution
  4. customwas then flushed with nitrogen
  5. customthe system was degassed once more
  6. customAfter flushing the system with nitrogen once more
  7. customthe flask was fitted with a jacketed reflux condenser
  8. customthe system was purged under vacuum once more
  9. customThe reaction mixture system was then flushed with nitrogen
  10. temperaturewarmed to 100° C
  11. stirringto stir overnight under nitrogen at elevated temperatures
  12. temperatureThe reaction was cooled to room temperature
  13. filtrationthe mixture was filtered through Celite
  14. washwashing heavily with ethyl acetate
  15. customThe liquid filtrate was then collected
  16. customthe solvent was removed under reduced pressure
  17. customabsorbing the residue onto Celite
  18. customThe product was then purified
  19. washeluting a gradient of 100% heptanes to 75% ethyl acetate in heptane

Sources & evidence

ORD record
ord-8d5b62a2cc7643e39553b31e6545864f
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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