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

HRID 1664089Notes

Reaction equation

HRID 1664089 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 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. 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 a slightly yellow oil, which solidify upon standing. If some impurities remains, the compound can be purified by following the acidic extraction followed by basic recovery as performed before for 2-phenyl-4-dimethylaminopyridine.

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. customThe crude compound was purified by column chromatography (SiO2, CHCl3

Sources & evidence

ORD record
ord-186a38ade19c4cca98b581aff246b0f3
Source dataset
uspto-grants-2011_10
Patent number
US08039124B2

Reaction notes

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