Potassium Phosphate, Tribasic → HCID 22495628, compound

HRID 1815883Notes

Reaction equation

HRID 1815883 reaction equation
[F:1][C:2]1[CH:3]=[C:4](Br)[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=1.C([O-])(=O)C.[K+].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][C:35](OS(C(F)(F)F)(=O)=O)=[CH:34][CH:33]1[CH3:46])=[O:31])([CH3:28])([CH3:27])[CH3:26]>O1CCCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1(P([Pd-4](P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OCC)C.C1(C)C=CC=CC=1>[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][C:35]([C:4]2[C:5]3[O:9][CH:8]=[CH:7][C:6]=3[CH:10]=[C:2]([F:1])[CH:3]=2)=[CH:34][CH:33]1[CH3:46])=[O:31])([CH3:28])([CH3:26])[CH3:27]

Participants

11

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517044Potassium AcetateHCID 221448167-Bromo-5-fluoro-1-benzofuranHCID 22495589HCID 22495589, compound2×

Product 1

HCID 22495628HCID 22495628, compoundYield 69.5%

Reagents, catalysts & solvents 6

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 178420553HCID 178420553, compoundCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

A flask purged of oxygen and under a nitrogen atmosphere was charged with 0.104 gm (0.482 mMol) 5-fluoro-7-bromobenzofuran, 0.184 gm (0.723 mMol) bis(pinacolato)di-boron, 0.0043 gm (0.0024 mMol) palladium(II) chloride, 0.016 gm (0.0029 mMol) 1,1′-bis(diphenylphosphino)ferrocene, 0.142 gm (1.45 mMol) potassium acetate, and 3 mL toluene. This mixture was heated at 90° C. for 5 hours and was then poured into 150 mL diethyl ether and filtered through a bed of celite. The filtrate was concentrated under reduced pressure to provide a dark residue. This material was dissolved in 3 mL tetrahydrofuran and the resulting solution purged of oxygen and placed under a nitrogen atmosphere. To this solution were added 0.028 gm (0.0024 mMol) tetrakis(triphenylphosphino)palladium(0), 0.153 gm (0.723 mMol) potassium phosphate, and 0.15 gm (0.434 mMol) 1-(tert-butoxycarbonyl)-2-methyl-4-trifluoromethylsulfonyloxy-1,2,5,6-tetrahydropyridine. The resulting mixture was stirred at reflux for 3.5 hours and was then charged with an additional 0.5 equivalents of 1-(tert-butoxycarbonyl)-2-methyl-4-trifluoromethylsulfonyloxy-1,2,5,6-tetrahydropyridine. The mixture was stirred at reflux for an additional 1.5 hours and was then poured into 150 mL diethyl ether. The mixture was filtered through a bed of celite and the filtrate concentrated under reduced pressure. The residue was dissolved in 2 mL dichloromethane and the solution was subjected to silica gel chromatography, eluting with a gradient of hexane containing 0-5% ethyl acetate. Fractions containing product were combined and concentrated under reduced pressure to provide 0.10 gm (62%) of the desired compound.

Workup

  1. customA flask purged of oxygen and under a nitrogen atmosphere
  2. filtrationfiltered through a bed of celite
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customto provide a dark residue
  5. customthe resulting solution purged of oxygen
  6. temperatureat reflux for 3.5 hours
  7. stirringThe mixture was stirred
  8. temperatureat reflux for an additional 1.5 hours
  9. filtrationThe mixture was filtered through a bed of celite
  10. concentrationthe filtrate concentrated under reduced pressure
  11. dissolutionThe residue was dissolved in 2 mL dichloromethane
  12. washeluting with a gradient of hexane containing 0-5% ethyl acetate
  13. additionFractions containing product
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c789f238257143b7a72043ac9dc87156
Source dataset
uspto-grants-2005_04
Patent number
US06881733B1

Reaction notes

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