Potassium Carbonate → HCID 57872776, compound

HRID 1664090Notes

Reaction equation

HRID 1664090 reaction equation
I[C:2]1[CH:7]=[C:6]([N:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][N:3]=1.[F:11][C:12]1[CH:13]=[C:14](B(O)O)[CH:15]=[C:16]([F:18])[CH:17]=1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.O.CCOCC.C1C=CC([P]([Pd]([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)=CC=1>[F:11][C:12]1[CH:13]=[C:14]([C:2]2[CH:7]=[C:6]([N:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][N:3]=2)[CH:15]=[C:16]([F:18])[CH:17]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 110861002-IODO-4-DIMETHYLAMINOPYRIDINE

Product 1

HCID 57872776HCID 57872776, compoundYield 47.4%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-iodo-4-dimethylaminopyridine (2.68 g, 10.8 mmol), 3,5-difluorophenylboronic acid (2.56 g, 16.2 mmol) and K2CO3 (6.7 g, 48.6 mmol) in toluene (60 ml) and water (10 ml) were degased with nitrogen for 15 minutes. Pd(PPh3)4 (800 mg, 0.66 mmol) was added and the resulting mixture was heated to 90° C. for 48 hours under nitrogen. After being cooled to room temperature, the aqueous phase was separated and extracted with EtOAc (3×100 ml). The combined organic fractions were washed with brine, dried over MgSO4, filtered and evaporated to afford a brown oil. The following oil was dissolved in Et2O and extracted with 10% HCl solution (3×50 ml). The combined aqueous fractions were washed with Et2O (2×100 ml) and neutralized with concentrated NaOH solution. The resulting mixture was extracted with EtOAc (4×100 ml), the combined organic fractions were washed with brine (50 ml), dried over MgSO4, filtered and evaporated to dryness. The obtained residue was then purified by column chromatography (SiO2, EtOAc) to afford 1.2 g (46%) of the titled compound as a colorless oil, which solidify upon standing. The crude compound was purified by column chromatography (SiO2, CHCl3 then CHCl3/MeOH, 97/3) to afford 1 g (40%) of the titled compound as a colorless oil, which solidify upon standing.

Workup

  1. customwere degased with nitrogen for 15 minutes
  2. temperatureAfter being cooled to room temperature
  3. customthe aqueous phase was separated
  4. extractionextracted with EtOAc (3×100 ml)
  5. washThe combined organic fractions were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto afford a brown oil
  10. extractionextracted with 10% HCl solution (3×50 ml)
  11. washThe combined aqueous fractions were washed with Et2O (2×100 ml) and neutralized with concentrated NaOH solution
  12. extractionThe resulting mixture was extracted with EtOAc (4×100 ml)
  13. washthe combined organic fractions were washed with brine (50 ml)
  14. dry with materialdried over MgSO4
  15. filtrationfiltered
  16. customevaporated to dryness
  17. customThe obtained residue was then purified by column chromatography (SiO2, EtOAc)

Sources & evidence

ORD record
ord-f3a865314a2c40a29afcccc89b0b2796
Source dataset
uspto-grants-2011_10
Patent number
US08039124B2

Reaction notes

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