Water → HCID 68279918, compound

HRID 525495Notes

Reaction equation

HRID 525495 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH:13]1[CH2:18][CH2:17][CH:16]([C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:15][CH2:14]1)[CH:6]=[N:5]2.[CH2:23]([O:25][C:26]([CH:28]1[CH2:33][CH2:32][N:31]([CH2:34][B-](F)(F)F)[CH2:30][CH2:29]1)=[O:27])[CH3:24].[K+].C(=O)([O-])[O-].[Cs+].[Cs+].O1CCCC1.O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:23]([O:25][C:26]([CH:28]1[CH2:33][CH2:32][N:31]([CH2:34][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[C:7]([O:12][CH:13]2[CH2:18][CH2:17][CH:16]([C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:15][CH2:14]2)[CH:6]=[N:5]3)[CH2:30][CH2:29]1)=[O:27])[CH3:24]

Participants

8

Reactant 6

HCID 962WaterHCID 8028TetrahydrofuranHCID 10796Cesium carbonate2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 68279539HCID 68279539, compoundHCID 129946453HCID 129946453, compound2×

Product 1

HCID 68279918HCID 68279918, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst2×

Conditions

Temperature
60 °C

Procedure

6-Bromo-2-(4-tert-butyl-cyclohexyloxy)-quinoxaline (0.2879 g, 0.0007925 mol), potassium ((4-(ethoxycarbonyl)piperidin-1-yl)methyl)trifluoroborate (0.4392 g, 0.001585 mol), palladium acetate (0.01068 g, 4.755E-5 mol) 2-(Dicyclohexylphosphino)-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (0.06800 g, 0.0001426 mol) and cesium carbonate (0.7746 g, 0.002377 mol) were added to a capped 40 mL vial equipped with a magnetic stir bar. The vial was degassed and purged with argon. Tetrahydrofuran (7.713 mL, 0.09510 mol) and water (1.142 mL, 0.06340 mol) were added and the reaction mixture was degassed, purged with argon then stirred at 60° C. for 24 hours. An additional 1 eq. of potassium ((4-(ethoxycarbonyl)piperidin-1-yl)methyl)trifluoroborate; 0.03 eq. of palladium acetate; 0.09 eq. of 2-(dicyclohexylphosphino)-2′,4′,6′-tri-isopropyl-1,1′-biphenyl and 1.5 eq. of cesium carbonate were added. The mixture was degassed, flushed with argon and heated at 60° C. overnight. The mixture was cooled to room temperature, diluted with ethyl acetate and washed with water, then brine. The layers were separated and the organic layer was dried over MgSO4, filtered, concentrated under reduced pressure and purified by flash chromatography (24 g SiO2 column; 0-10% MeOH in methylene chloride) to give the title compound. ESI-MS (M+H+): 454.1

Workup

  1. customvial equipped with a magnetic stir bar
  2. customThe vial was degassed
  3. custompurged with argon
  4. customthe reaction mixture was degassed
  5. custompurged with argon
  6. customThe mixture was degassed
  7. customflushed with argon
  8. temperatureheated at 60° C. overnight
  9. temperatureThe mixture was cooled to room temperature
  10. additiondiluted with ethyl acetate
  11. washwashed with water
  12. customThe layers were separated
  13. dry with materialthe organic layer was dried over MgSO4
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. custompurified by flash chromatography (24 g SiO2 column; 0-10% MeOH in methylene chloride)

Sources & evidence

ORD record
ord-6f8670d6cc0d4693bb2e692f0e92f413
Source dataset
uspto-grants-2016_05
Patent number
US09340527B2

Reaction notes

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