Potassium Carbonate → 2-(2,4-Difluorophenyl)-N,N-dimethylpyridin-4-amine

HRID 874090Notes

Reaction equation

HRID 874090 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:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1B(O)O.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.O.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:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[C:2]1[CH:7]=[C:6]([N:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 110861002-IODO-4-DIMETHYLAMINOPYRIDINE

Product 1

HCID 208073522-(2,4-Difluorophenyl)-N,N-dimethylpyridin-4-amineYield 78.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-iodo-4-dimethylaminopyridine (3 g, 12 mmol), 2,4-difluorophenylboronic acid (2.3 g, 14.5 mmol) and K2CO3 (6 g 43.5 mmol) in toluene (60 ml) and water (10 ml) were degassed 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 further purify the compound the so-obtained 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 aqueous 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 crude compound was purified by column chromatography (SiO2, CHCl3 then CHCl3/MeOH, 97/3) to afford 2.2 g (78%) of the titled compound as slightly yellow oil which solidified upon standing.

Workup

  1. customwere degassed 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 further purify the compound the so-obtained oil
  10. dissolutionwas dissolved in Et2O
  11. extractionextracted with 10% HCl solution (3×50 ml)
  12. washThe combined aqueous fractions were washed with Et2O (2×100 ml) and neutralized with concentrated NaOH aqueous solution
  13. extractionThe resulting mixture was extracted with EtOAc (4×100 ml)
  14. washthe combined organic fractions were washed with brine (50 ml)
  15. dry with materialdried over MgSO4
  16. filtrationfiltered
  17. customevaporated to dryness
  18. customThe crude compound was purified by column chromatography (SiO2, CHCl3

Sources & evidence

ORD record
ord-49f98f7020db42a2b4ac54aca209e592
Source dataset
uspto-grants-2015_03
Patent number
US08980440B2

Reaction notes

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